Skip to main content
Log in

Clinical Pharmacokinetics of the Antituberculosis Drugs

  • Review Articles
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

The quantitative aspects of the disposition in man of 12 antituberculosis drugs [isoniazid, rifampicin, (rifampin), ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin, ethionamide, cycloserine, capreomycin, viomycin and thiacetazone] are reviewed. Isoniazid appears to be the only agent for which plasma concentrations and clearance are related to hereditary differences in acetylator status and for which there is an appreciable ‘first-pass’ effect. Recent data cast doubt on the suggestion that isoniazid may be more hepatotoxic for rapid as opposed to slow acetylators. Continuous administration of rifampicin leads to induction of enzymes in the liver with a concomitant decrease in maximum plasma concentrations, the time required to achieve this level, elimination half-life, and area under the plasma concentration-time curve (AUC). Coadministration of para-aminosalicylic acid leads to increases in the serum concentrations and elimination half-life of isoniazid.

With a few exceptions, the metabolites of the antituberculosis drugs are devoid of antimicrobial activity; the exceptions are 25-desacetylrifampicin which accounts for approximately 80% of the drug’s antimicrobial activity in human bile, the acetylated and glycylated metabolites of para-aminosalicylic acid, and the sulphoxide metabolites of ethionamide.

The effect of renal impairment is relatively unimportant for the excretion of isoniazid, rifampicin and para-aminosalicylic acid, but the elimination half-life of streptomycin increases to 100 hours when the blood urea nitrogen level is greater than 100mg/100ml, and ototoxicity is strikingly more frequent. In states of malnutrition, such as kwashiorkor, the protein binding of para-aminosalicylic acid decreases from 15% to essentially zero and in the case of ethionamide and streptomycin binding decreases by 6% and 16% respectively. Of the data concerning age-related effects, most notable are the prolonged elimination half-life of isoniazid in neonates (up to 19.8 hours), and the lower peak serum concentrations of rifampicin in children of one-third to one-tenth those of adults following a similar dose on a weight basis. For kanamycin, the maximum plasma concentration varies inversely with age but is not influenced by birthweight; however, the clearance is directly dependent upon birthweight and postnatal age. For the elderly, age is an insignificant factor for the elimination of isoniazid when compared with young adults of similar acetylator status, and the metabolism of rifampicin may be considered globally unaltered in this age group. The elimination half-life of kanamycin increases from 107 minutes in younger individuals to 282 minutes in elderly populations.

Recent data indicate that isoniazid, rifampicin, ethambutol, para-aminosalicylic acid, pyrazinamide, streptomycin, kanamycin and cycloserine appear in measurable quantities in breast milk, with isoniazid having the highest recorded level of 2.3% of a daily administered dose.

Pharmacokinetic drug interactions and techniques for therapeutic drug monitoring of each of these agents (and some of their metabolites) are also briefly reviewed. Consideration of the pharmacokinetics of these drugs in planning treatment regimens could lead to more rational, safer and possibly more efficacious use.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abramowicz, M. (Ed.): Drugs for tuberculosis. Medical Letter 24: 17–19 (1982).

    Google Scholar 

  • Acocella, G.: Untersuchung über Metabolismus und Kinetik der Kombination Rifampicin-Isoniazid. Proceedings of the Prague Symposium 2: 32–37 (1970).

    Google Scholar 

  • Acocella, G.: Clinical pharmacokinetics of rifampicin. Clinical Pharmacokinetics 3: 108–127 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Acocella. G.: Bonollo, L.; Garimold, M.; Mainardi, M.; Tenconi, L.T. and Nicolis, F.B.: Kinetics of rifampicin and isoniazid administered alone and in combination to normal subjects and patients with liver disease. Gut 13: 47–53 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Acocella, G. and Conti, R.: Interaction of rifampicin with other drugs. Tubercle 61: 171–177 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Acocella, G.; Mattiussi, R. and Segre, G.: Multi-compartmental analysis of serum, urine and bile concentrations of rifampicin and desacetylrifampicin in subjects treated for one week. Pharmacological Research Communications 10: 271–288 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Acocella. G. and Scotti, R.: Kinetic studies on the combination of rifampicin-trimethoprim in man. Journal of Antimicrobial Chemotherapy 2: 271–277 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Adcock. J.D. and Hettig. R.A.: Absorption, distribution and excretion of streptomycin. Archives of Internal Medicine 77: 179–195 (1946).

    Article  PubMed  CAS  Google Scholar 

  • Advenier, C.; Gobert, C.; Houin, G.: Bidet, D.; Richelet, S. and Tillement, J.P.: Pharmacokinetic studies of rifampicin in the elderly. Therapeutic Drug Monitoring 5: 61–65 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Advenier. C.; Saint-Aubin, A.; Gobert, C.; Houin, G.; Albengres, E. and Tillement. J.P.: Pharmacokinetics of isoniazid in the elderly. British Journal of Clinical Pharmacology 10: 167–169 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Ahmad, D.; Mathur. P.: Ahuja, S.; Henderson, R. and Carruthers, G.: Rifampicin-quinidine interaction. British Journal of Chest Disease 73: 409–411 (1979).

    Article  CAS  Google Scholar 

  • Akbani, Y.; Bolme, P.; Lindblad, B.S. and Rahimtoola, R.J.: Control of streptomycin and isoniazid in malnourished children treated for tuberculosis. Acta Paediatrica Scandinavica 66: 237–240 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, D.G. and Jewell, M.: The absorption, excretion and toxicity of streptomycin in man. New England Journal of Medicine 233: 485–491 (1945).

    Article  Google Scholar 

  • Archer, G.L.; Armstrong, B.C. and Kline, B.J.: Rifampin blood and tissue levels in patients undergoing cardiac valve surgery. Antimicrobial Agents and Chemotherapy 21: 800–803 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Archer, G.J.; Henderson, C. and Grace, P.M.: Antituberculosis drugs in children. Lancet 2: 1025–1026 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Axline, S.G. and Simon, H.J.: Clinical pharmacology of antimicrobials in premature infants. I. Kanamycin, streptomycin and neomycin. Antimicrobial Agents and Chemotherapy 35: 135–139 (1965).

    Google Scholar 

  • Bang, H.O. and Strandgaard, E.: Continued studies on the para-aminosalicylic acid concentration in the blood during treatment with various para-aminosalicylic acid preparations. Acta Tuberculosis Scandinavica 35: 173–196 (1958).

    Google Scholar 

  • Barry, V.C.: Chemotherapy of Tuberculosis (Butterworth, London 1968).

    Google Scholar 

  • Bass, J.B. and Hawkins, E.L.: Treatment of disease caused by nontuberculosis myobacteria. Archives of Internal Medicine 143: 1439–1441 (1983).

    Article  PubMed  Google Scholar 

  • Beachler, C.W.; Speer, M.E.; Mason, E.O. and Yow, M.D.: Pharmacology of kanamycin in the newborn. Southern Medical Journal 75: 301–305 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Bennett, P.N.; John, V.A. and Whitmarsh, V.B.: Effect of rifampicin on metoprolol and antipyrine kinetics. British Journal of Clinical Pharmacology 13: 387–391(1982).

    Article  PubMed  CAS  Google Scholar 

  • Bergrem, H. and Refvem, O.K.: Altered prednisolone pharmacokinetics in patients treated with rifampicin. Acta Medica Scandinavica 213: 339–344 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Bernstein, J.; Lott, W.A.; Steinberg, B.A. and Yale, H.L.: Chemotherapy of experimental tuberculosis. V. Isonicotinic acid hydrazide (nydrazid) and related compounds. American Review of Tuberculosis 65: 357–363 (1952).

    PubMed  CAS  Google Scholar 

  • Bernstein, R.E.: Isoniazid hepatoxicity and acelylalion during tuberculosis chemoprophylaxis. American Review of Respiratory Disease 121: 429–430 (1980).

    Google Scholar 

  • Bernstein, R.E.: The hepatotoxicity of isoniazid among the three acetylator phenotypes. American Review of Respiratory Disease 123: 568 (1981).

    Google Scholar 

  • Bieder, A.; Brunei, P. and Mazeau, L.: Identification de trois nouveaux metabolites de rethionamide: Chromatographie, spectrophotometrie, polarographie. Annales Pharmaceutiques Francaises 24: 493–500 (1966).

    PubMed  CAS  Google Scholar 

  • Bistritzer. T.; Barzilay, Z. and Jonas, A.: Isoniazid-rifampicin-induced fulminant liver disease in an infant. Journal of Pediatrics 97: 480–482 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Black, H.R.; Griffith, R.S. and Peabody, A.M.: Absorption, excretion and metabolism of capreomycin in normal and diseased states. Annals of the New York Academy of Sciences 135: 974–982 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Black, M.; Mitchell. J.R.; Zimmerman, H.J.; Ishak, K.G. and Epler, G.R.: Isoniazid associated hepatitis in 114 patients. Gastroenterology 69: 289–302 (1975).

    PubMed  CAS  Google Scholar 

  • Block. S.H.: Carbamazepine-isoniazid interaction. Pediatrics 69: 494–495 (1982).

    PubMed  CAS  Google Scholar 

  • Bobrowitz, I.D.: Ethambutol in the retreatment of pulmonary tuberculosis. Annals of the New York Academy of Sciences 135: 796–801 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Bobrowitz, I.D.: Ethambutoi compared to streptomycin in original treatment of advanced pulmonary tuberculosis. Chest 60: 14–21 (1970).

    Article  Google Scholar 

  • Bobrowilz, I.D.: Ethambutol-isoniazid versus streptomycin-ethambutol-isoniazid in original treatment of cavitary tuberculosis. American Review of Respiratory Disease 109: 548–553 (1974).

    Google Scholar 

  • Boman, G.: Serum concentrations and half-life of rifampicin after simultaneous oral administration of aminosalicylic acid or isoniazid. European Journal of Clinical Pharmacology 7: 217–225 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Boman, G.; Borga, O.: Hanngren, A.; Malmborg, A.S. and Sjöqvist, F.: Blood levels of rifampicin, para-aminosalicylic acid and isoniazid after single oral doses separately and in combination in man. Proceedings of the Prague Symposium 2: 44–47 (1970).

    Google Scholar 

  • Boman, G.: Eliasson, K. and Odar-Cederlöf, I.: Acute cardiac failure during treatment with digitoxin. An interaction with rifampicin. British Journal of Clinical Pharmacology 10: 89–90 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Boman, G.; Hanngren, A.; Malmborg, A.S.; Borga, O. and Sjöqvist, F.: Drug interaction: Decreased serum concentrations of rifampicin when given with para-aminosalicylic acid. Lancet 1: 800 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Boman, G.; Lundgren, P. and Stjernstrom, G.: Mechanisms of the inhibitory effect of para-aminosalicylic acid granules on the absorption of rifampicin: Absorption of rifampicin by excipient bentonite. European Journal of Pharmacology 8: 293–300 (1975).

    Article  CAS  Google Scholar 

  • Boman, G. and Malmborg, A.S.: Rifampicin in plasma and pleural fluid after single oral doses. European Journal of Clinical Pharmacology 7: 51–58 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Borowiecka, B.: Spectrophotometric and chromatographic determinations of kanamycin A in pharmaceutical preparations. Polish Journal of Pharmacology and Pharmacy 28: 353–359 (1976).

    PubMed  CAS  Google Scholar 

  • Brodie, M.J.; Boobis, A.R.; Hillyard, C.J.; Abeyasekera, G.; MacIntyre, I. and Park, B.K.: Effect of isoniazid on vitamin D metabolism and hepatic monooxygenase. Clinical Pharmacology and Therapeutics 30: 363–367 (1980a).

    Google Scholar 

  • Brodie, M.J.; Boobis, A.R.; Dollery, C.T.; Hillyard, C.J.; Brown, D.J.; MacIntyre, I. and Park, B.K.: Rifampicin and vitamin D metabolism. Clinical Pharmacology and Therapeutics 30: 810–814 (1980b).

    Google Scholar 

  • Brodie, M.J.; Boobis, A.R.; Hillyard, C.J.; Abeyasekera, G.; Stevenson, J.C.; MacIntyre, I, and Park, B.K.: Effect of rifampicin and isoniazid on vitamin D metabolism. Clinical Pharmacology and Therapeutics 32: 525–530 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Bruce, R.M. and Wise, L.: Tuberculosis after jejunoileal bypass for obesity. Annals of Internal Medicine 87: 574–576 (1976).

    Google Scholar 

  • Buchanan, N.: Streptomycin and isoniazid metabolism in malnourished children. Acta Pediatrica Scandinavica 66: 663 (1977).

    Article  CAS  Google Scholar 

  • Buchanan, N. and van der Walt, L.A.: The binding of antituberculosis drugs to normal and kwashiorkor serum. South African Medical Journal 52: 522–525 (1977).

    PubMed  CAS  Google Scholar 

  • Buggs, C.W.; Pilling, M.A.; Bronstein, B.; Hirschfeld, J.W.; Worznik, L. and Key, L.J.: The absorption, distribution and excretion of streptomycin in man. Journal of Clinical Investigation 25: 94–102 (1946).

    Article  PubMed  CAS  Google Scholar 

  • Buniva, G.; Pagani, V. and Carozzi, A.: Bioavailability of rifampicin capsules. International Journal of Clinical Pharmacology, Therapy and Toxicology 21: 404–409 (1983).

    CAS  Google Scholar 

  • Buniva, G.; Palminteri, R. and Berti, M.: Kinetics of a rifampicin-trimethoprim combination. International Journal of Clinical Pharmacology and Biopharmacy 17: 256–259 (1979).

    PubMed  CAS  Google Scholar 

  • Cabana, B.E. and Taggart, J.G.: Comparative pharmacokinetics of BB-K8 and kanamycin in dogs and humans. Antimicrobial Agents and Chemotherapy 3: 478–483 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Caccio, P.A.: Spectrophotometric determination of pyrazinamide blood concentrations and excretion through the kidneys. American Review of Respiratory Disease 75: 105–112 (1957).

    Google Scholar 

  • Christopher, T.G.; Blair, A.; Forrey, A. and Cutler, R.E.: Kinetics of ethambutol elimination in renal disease. Proceedings of the Dialysis Transplant Forum 3: 96–100 (1973).

    CAS  Google Scholar 

  • Cohen, S.; Baumgartner, R.; Steinberg, M. and Weber, W.: Changes in the physicochemical characteristics of rabbit liver N-acetyltransferase during post-natal development. Biochimica et Biophysica Acta 304: 473–481 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Cohen, S. and Weber, W.: Newborn infants of tuberculosis mothers — further comment. Pediatrics 43: 303 (1969).

    PubMed  CAS  Google Scholar 

  • Colston, M.J.; Ellard, G.A. and Gammon, P.T.: Drugs for combined therapy: Experimental studies on the antileprosy activity of ethionamide and prothionamide, and a general review. Leprosy Review 49: 115–126 (1978a).

    PubMed  CAS  Google Scholar 

  • Colston, M.J.; Hilson, G.R.F.; Ellard, G.A. and Gammon, P.T.: The activity of thiacetazone, thiambutosine, thiocarbide and sulphamethoxypyridazine against Mycobacterium leprae in mice. Leprosy Review 49: 101–113 (1978b).

    PubMed  CAS  Google Scholar 

  • Conzelman, G.M.: The physiological disposition of cycloserine in the human subject. American Review of Tuberculosis and Pulmonary Disease 74: 739–746 (1956).

    CAS  Google Scholar 

  • Curci, C.: Pharmacological considerations of cycloserine. Scandinavian Journal of Respiratory Disease 71: 101–105 (1970).

    Google Scholar 

  • Danish, M.; Schultz, R. and Jusko, W.J.: Pharmacokinetics of gentamicin and kanamycin during hemodialysis. Antimicrobial Agents and Chemotherapy 6: 841–847 (1974).

    Article  PubMed  CAS  Google Scholar 

  • De Simoni, G. and Lucchesi, M.: Treatment of human tuberculosis with d-2,2′-(ethylenediamino)-di-1-butanol (ethambutol). Tipografia Operaia Romania, Rome 1966.

    Google Scholar 

  • Doluisio, J.T.; Dittert, L.W. and La Piana, J.C.: Pharmacokinetics of kanamycin following intramuscular administration. Journal of Pharmacokinetics and Biopharmaceutics 1: 253–265 (1973).

    Article  CAS  Google Scholar 

  • Donomae, I. and Yamamoto, K.: Clinical evaluation of ethambutol in pulmonary tuberculosis. Annals of the New York Academy of Sciences 135: 849–855 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Driessen, O.M.; Sorgedrager, N.; Michel, M.F.; Kerrebyin, K.F. and Herman, J.: Pharmacokinetic aspects of therapy with ampicillin and kanamycin in new born infants. European Journal of Clinical Pharmacology 13: 449–457 (1978).

    Article  Google Scholar 

  • Dume, T.H.; Wagner, C.L. and Wetzel, E.: Pharmacokinetics of ethambutol in healthy subjects and patients with terminal renal failure. Deutsche Medizinische Wochenschrift 96: 1430–1434 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Edius, L. and Harnanansingh, A.M.: A more sensitive spectrophotometric method for determination of isoniazid in serum or plasma. Clinical Chemistry 17: 492–494 (1971).

    Google Scholar 

  • Ellard, G.A.: Absorption, metabolism and excretion of pyrazinamide in man. Tubercle (London) 50: 144–158 (1969).

    Article  CAS  Google Scholar 

  • Ellard, G.A.; Dickerson, J.M.; Gammon, P.T. and Mitchison, D.A.: Serum concentrations and antituberculosis activity of thiacetazone. Tubercle 55: 41–54 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Ellard, G.A. and Gammon, P.T.: Pharmacokinetics of isoniazid metabolism in man. Journal of Pharmacokinetics and Biopharmaceutics 4: 83–113 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Ellard, G.A.; Gammon, P.T.; Lakshmenarayan, S.; Fox, W.; Aber, V.R.; Mitchison, D.A.; Citron, K.M. and Toll, R.: Pharmacology of some slow-release preparations of potential use in intermittent treatment of tuberculosis. Lancet 1: 340–343 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Ellard, G.A.; Girling, D.J. and Nunn, A.J.: The hepatoxicity of isoniazid among the three acetylator phenotypes. American Review of Respiratory Disease 132: 568 (1981).

    Google Scholar 

  • Ellard, G.A. and Haslam, R.M.: Observations on the reduction of the renal elimination of urate in man caused by the administration of pyrazinamide. Tubercle 57: 97–103 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Emmerson, A.M.; Gruneberg, R.N. and Johnson, E.S.: The pharmacokinetics in man of a combination of rifampicin and trimethoprim. Journal of Antimicrobial Chemotherapy 4: 523–531 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Eule, H.: PAS. Tubercle 54: 165–167 (1973).

    Article  Google Scholar 

  • Fox, H.H.: The chemical approach to the control of tuberculosis. Science 116: 129–131 (1952).

    Article  PubMed  CAS  Google Scholar 

  • Fox, H.H.; Stark, A.J.; Tall, R.; Bhatia, J.L.; Clarke, J.H.C.; Donea, T.O.; Krishnaswami, K..V. and Oussedik, N.: A study of adverse reactions to high dose intermittent thiacetazone. Tubercle 55: 29–40 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Gangadharam, F.R.J. and Candler, E.R.: Microbiological assay of ethambutol. Journal of Antimicrobial Chemotherapy 3: 57–63 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Garcia, G.; de Vidal, E.L. and Triyillo, H.: Serum levels and urinary concentration of kanamycin, bekanamycin and amikacin (BB-K8) in diabetic children and a control group. Journal of International Medical Research 5: 322–329 (1977).

    PubMed  CAS  Google Scholar 

  • Garnham, J.C.; Taylor, T.; Turner, P. and Chasseaud, L.F.: Serum concentrations and bioavailability of rifampicin and isoniazid in combination. British Journal of Clinical Pharmacology 3: 897–902 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Garrod, L.P. and O’Grady, F. (Eds): Antibiotics and Chemotherapy, p. 105 (Williams and Wilkins, Baltimore 1971).

    Google Scholar 

  • Girling, D.J.: Adverse effects of antituberculosis drugs. Drugs 23: 56–74 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Gold, C.H.; Buchanan, N.; Tringham, V.; Viljoen, M.; Strickwold, B. and Moodley, G.P.: Isoniazid pharmacokinetics in patients in chronic renal failure. Clinical Nephrology 6: 365–369 (1976).

    PubMed  CAS  Google Scholar 

  • Good, R.G. and Johnson, G.H.: The placental transfer of kanamycin during late pregnancy. Obstetrics and Gynecology 38: 60–62 (1971).

    PubMed  CAS  Google Scholar 

  • Greenberg, P.A. and Sanford, J.P.: Removal and absorption of antibiotics in patients with renal failure undergoing peritoneal dialysis. Annals of Internal Medicine 66: 465–477 (1967).

    PubMed  CAS  Google Scholar 

  • Gundert-Remy, U.; Klett, M. and Weber, E.: Concentration of ethambutol in cerebrospinal fluid in man as a function of the non-protein-bound drug fraction in serum. European Journal of Clinical Pharmacology 6: 133–136 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Gurumurthy, P.; Krishnamurthy, M.S.; Nazareth, O.; Parthasarathy, R.; Sarma, G.R.; Somasundaram, P.R.; Tripathy, S.P. and Ellard, G.A.; Lack of relationship between hepatic toxicity and acetylator phenotype in three thousand South Indian patients during treatment with isoniazid with tuberculosis. American Review of Respiratory Disease 129: 58–61 (1984).

    PubMed  CAS  Google Scholar 

  • Gyselen, A.; Verbist, L.; Prignot, J. and Cosemans, J.: Capreomycin in the retreatment of patients with pulmonary tuberculosis. Tubercle (London) 46: 243–249(1965).

    Article  CAS  Google Scholar 

  • Hagelund, C.H.; Wahlen, P. and Eidsaunet, W.: Absorption of rifampicin in gastrectomized patients. Effects of meals. Scandinavian Journal of Respiratory Disease 58: 241–246 (1977).

    CAS  Google Scholar 

  • Hansten, P.D.: Isoniazid drug interactions. Drug Interactions Newsletter 3: 7–12 (1983).

    Google Scholar 

  • Hein, D.W. and Weber, W.W.: Polymorphic N-acetylation of phenelzine and monoacetylhydrazine by highly purified rabbit liver isoniazid N-acetyltransferase. Drug Metabolism and Disposition 10: 225–229 (1982).

    PubMed  CAS  Google Scholar 

  • Held, H. and Fried, F.: Elimination of para-aminosalicylic acid in patients with liver disease and renal insufficiency. Chemotherapy 23: 405–415 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Herman, R.J.; Nakamura, K.; Wilkinson, G.R. and Wood, A.J.: Induction of propranolol metabolism by rifampicin. British Journal of Clinical Pharmacology 16: 565–569 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Herngren, L.; Boreus, L.O.; Jolling, B. and Lagercrantz, R.: Pharmacokinetic aspects of streptomycin treatment of neonatal septicemia. Scandinavian Journal of Infectious Disease 9: 301–308 (1977).

    CAS  Google Scholar 

  • Holdiness, M.R.: Chromatographic analysis of neurotransmitters and antitubercular drugs. PhD Dissertation, Emory University, Atlanta, Georgia (1981).

    Google Scholar 

  • Holdiness, M.R.: High pressure liquid chromatograp determination of isoniazid and acetylisoniazid in human plasma. Journal of Liquid Chromatography 5: 707–714 (1982).

    Article  CAS  Google Scholar 

  • Holdiness, M.R.: Mycobacterial colonization. Archives of Internal Medicine 144: 653–654 (1984a).

    Article  PubMed  CAS  Google Scholar 

  • Holdiness, M.R.: Breast feeding and antituberculosis drugs. Archives of Internal Medicine 144: 1888 (1984b).

    Article  PubMed  CAS  Google Scholar 

  • Holdiness, M.R.: Chromatographic analysis of antituberculosis drugs in biological samples. Journal of Chromatography — Biomedical Applications (In press, 1985).

  • Holdiness, M.R.; Israili, Z.H. and Justiv, J.B.: Gas chromatographic mass spectrometric determination of ethambutol in human plasma. Journal of Chromatography — Biomedical Applications 224: 415–422 (1981).

    Article  CAS  Google Scholar 

  • Honigberg, I.L.; Stewart, J.T.; Clark, T.C. and Davis, D.Y.: Non-extractive fluorometric measurement of para-aminosalicylic acid in plasma by ion-pairing techniques and high performance liquid chromatography. Journal of Chromatography — Biomedical Applications 181: 266–271 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Horai, Y.; Ishizoki, T.; Sasaki, T.; Koya, G.; Matsuyama, K. and Iguchi, S.: Isoniazid disposition, comparison of isoniazid phenotyping methods in an acetylator distribution of Japanese patients with idiopathic systemic lupus erythematosus and control subjects. British Journal of Clinical Pharmacology 13: 361–374 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Houin, G.; Beucler, A.; Richelet, S.; Brioride, R.; Lafaix, C.H. and Tillement, J.P.: Pharmacokinetics of rifampicin and desacetylrifampicin in tuberculosis patients after different rates of infusion. Therapeutic Drug Monitoring 5: 67–72 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Howard, J.B. and McCracken, G.H.: Reappraisal of kanamycin usage in neonates. Journal of Pediatrics 86: 949–956 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Hutchings, A.; Monie, R.D.; Spragg, B. and Routledge, P.A.: High performance liquid chromatographic analysis of isoniazid and acetylisoniazid in biological fluids. Journal of Chromatography — Biomedical Applications 227: 385–390 (1983).

    Article  Google Scholar 

  • Jeanes, C.W.L.; Jessamine, A.G. and Eidus, L.: Treatment of chronic drug resistant pulmonary tuberculosis with rifampicin and ethambutol. Canadian Medical Association Journal 106: 884–888 (1972).

    PubMed  CAS  Google Scholar 

  • Jenner, P.J.: High performance liquid chromatographic determination of thiacetazone in body fluids. Journal of Chromatography — Biomedical Applications 276: 463–470 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Jenner, P.J. and Ellard, G.A.: High performance liquid chromatographic determination of ethionamide and prothionamide in body fluids. Journal of Chromatography — Biomedical Applications 225: 245–251 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Jenner, P.J.; Ellard, G.A.; Gruer, P.K.J. and Aber, V.R.: A comparison of the blood levels and urinary excretion of ethionamide and prothionamide in man. Journal of Antimicrobial Chemotherapy 13: 267–277 (1984a).

    Article  PubMed  CAS  Google Scholar 

  • Jenner, P.J.; Ellard, G.A. and Swai, O.B.: A study of thiacetazone blood levels and urinary excretion in man using high performance liquid chromatography. Leprosy Review 55: 121–128 (1984b).

    PubMed  CAS  Google Scholar 

  • Kenny, M.T. and Strates, B.: Metabolism and pharmacokinetics of the antibiotic rifampicin. Drug Metabolism Reviews 12: 159–218 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Kirby, W.M.; Clarke, J.T.; Libke, R.D. and Regamey, C.: Clinical pharmacology of amikacin and kanamycin. Journal of Infectious Diseases 134: S312–S315 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Kiss, I.J.; Farago, E.; Juhasz, I.; Bacsa, S. and Fabian, E.: Investigation on the serum and lung tissue level of rifampicin in man. Journal of Clinical Pharmacology 13: 42–47 (1976).

    CAS  Google Scholar 

  • Kiss, I.J.; Farago, E.; Kiss, B. and Varhelyi, L.: Pharmacokinetic study of rifampicin in biliary surgery. International Journal of Clinical Pharmacology 16: 105–109 (1978).

    CAS  Google Scholar 

  • Kopenen, A.; Mantyla, R.; Klinge, E.; Nykanen, S.; Männistö, P. and Lamminsivu, U.: Influence of diet on the rate and extent of bioavailability of isoniazid. Acta Pharmacologica et Toxicologica 4: 75–83 (1981).

    Google Scholar 

  • Kreukniet, J.; Blom Van Assendelft, P.M.; Mouton, P.R.; Tasman, A. and Bangma, P.J.: The influence of para-aminosalicylic acid on isonicotinic acid hydrazide blood levels after oral and intravenous administration. Scandinavian Journal of Respiratory Disease 47: 236–243 (1967).

    Google Scholar 

  • Kristensen, M.; Hansen, J.M.; Kampmann, J.; Lumholtz, B. and Siersbaek-Nielsen, K.: Drug elimination and renal function. Journal of Clinical Pharmacology 14: 307–308 (1974).

    PubMed  CAS  Google Scholar 

  • Kunin, C.M.: Absorption, distribution, excretion and fate of kanamycin. Annals of the New York Academy of Sciences 132: 811–817 (1965).

    Article  Google Scholar 

  • Lavisgne, J.G.; d’Auteuil, A.B. and Delays, J.M.: Para-aminosalicylate metabolism in cancer patients sensitive and resistant to chemotherapy. British Journal of Cancer 35: 580–585 (1977).

    Article  Google Scholar 

  • Lecaillon, J.B.; Febvre, N.; Metayer, J.P. and Souppart, C.: Quantitative assay of rifampicin and three of its metabolites in human plasma, urine and saliva by high performance liquid chromatography. Journal of Chromatography — Biomedical Applications 145: 319–324 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Lee, C.S. and Benet, L.Z.: Micro and macro GLC determination of ethambutol in biological fluids. Journal of Pharmaceutical Sciences 67: 470–473 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Lee, C.S.; Brater, D.C.; Gambertoglio, J.G. and Benet, L.Z.: Disposition kinetics of ethambutol in man. Journal of Pharmacokinetics and Biopharmaceutics 8: 335–346 (1980a).

    Article  PubMed  CAS  Google Scholar 

  • Lee, C.S.; Gambertoglio, J.G.; Barter, D.C. and Benet, L.Z.: Kinetics of oral ethambutol in the normal subject. Clinical Pharmacology and Therapeutics 22: 615–621 (1978).

    Google Scholar 

  • Lee, C.S.; Marbury, T.C. and Benet, L.Z.: Clearance calculations in hemodialysis: Application to blood, plasma, dialysate measurements for ethambutol. Journal of Pharmacokinetics and Biopharmaceutics 8: 69–81 (1980b).

    Article  PubMed  Google Scholar 

  • Lees, A.W.: Ethionamide and isoniazid in previously untreated cases of pulmonary tuberculosis. Diseases of the Chest 45: 247–251 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Lehmann, J.: The role of metabolism of para-aminosalicylic acid in the treatment of tuberculosis. Scandinavian Journal of Respiratory Disease 50: 169–185 (1969).

    CAS  Google Scholar 

  • Levi, A.J.; Sherlock, S. and Walker, D.: Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet 1: 1275 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Liss, R.H.; Letourneau, R.J. and Schepis, J.P.: Distribution of ethambutol in primate tissues and cells. American Review of Respiratory Disease 123: 529–532 (1981).

    PubMed  CAS  Google Scholar 

  • Llorens, J.; Serrano, R.J. and Sanchez, R.: Pharmacodynamic interference between rifampicin and isoniazid. Chemotherapy 24: 97–103 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Lloyd, J. and Mitchison, D.A.: A vertical diffusion method for the microbiological assay of isoniazid. Journal of Clinical Pathology 17: 622–626 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Malspeis, L. and Gold, D.: Stability of cycloserine in buffered aqueous solutions. Journal of Pharmaceutical Sciences 53: 1173–1180 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Männistö, P.: Absorption of rifampin from various preparations and pharmaceutic forms. Clinical Pharmacology and Therapeutics 21: 370–374 (1976).

    Google Scholar 

  • Männistö, P.; Mäntylö, R.; Klinge, E.; Nykänen, S.; Koponen, A. and Lamminsivu, U.: Influence of various diets on the bio-availability of isoniazid. Journal of Antimicrobial Chemotherapy 10: 427–434 (1982).

    Article  PubMed  Google Scholar 

  • Mattila, M.J.; Friman, A.; Larmi, T.K.I. and Koshinen, R.: Absorption of ethionamide, isoniazid and aminosalicylic acid from the post-resection gastrointestinal tract. Annales Medicinae Internae Fenniae 47: 209–212 (1969b).

    CAS  Google Scholar 

  • Mattila, M.J.; Linnoila, M.; Seppälä, T. and Koskinen, R.: Effects of aluminium hydroxide and glycopyrronium on the absorption of ethambutol and alcohol in man. British Journal of Clinical Pharmacology 5: 161–166 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Mattila, M.J.; Nieminen, E. and Tiitinen, H.: Serum levels, urinary excretion, and side effects of cycloserine in the presence of isoniazid and para-aminosalicylic acid. Scandinavian Journal of Respiratory Disease 50: 291–300 (1969a).

    CAS  Google Scholar 

  • Mays, D.L.; Van Apeldoorn, R.J. and Lauback, R.G.: High performance liquid chromatographic determination of kanamycin. Journal of Chromatography 120: 93–102 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Mazze, R.I.; Woodruff, R.E. and Heerdt, M.E.: Isoniazid induced enflurane deflorination in humans. Anesthesiology 57: 5–8 (1982).

    Article  PubMed  CAS  Google Scholar 

  • McAllister, W.A.C.; Thompson, P.J.; Al-Habet, S.M. and Rogers, H.J.: Rifampicin reduces the effectiveness and bioavailability of prednisolone. British Medical Journal 286: 923–925 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Meisel, S. and Brower, R.: Rifampicin: A suicidal dose. Annals of Internal Medicine 92: 262–263 (1980).

    PubMed  CAS  Google Scholar 

  • Miceli, J.N.; Olson, W.A. and Cohen, S.N.: Elimination kinetics of isoniazid in the newborn infant. Development Pharmacology and Therapeutics 2: 235–239 (1981).

    CAS  Google Scholar 

  • Miller, R.R.; Porter, J. and Greenblatt, D.J.: Clinical importance of the interaction of phenytoin and isoniazid. Chest 75: 356–358 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Mitchell, J.R.; Thorgeirsson, U.P.; Black, M.; Timbrell, J.A.; Snodgrass, W.R.; Potter, W.Z.; Jollon, D.J. and Kasen, H.R.: Increased incidence of isoniazid hepatitis in rapid acetylators: Possible relationship to hydrazine metabolites. Clinical Pharmacology and Therapeutics 18: 70 (1976).

    Google Scholar 

  • Mouton, R.P.; Mattie, H.; Swart, K.; Kreukniet, J. and Wael, J.: Blood levels of rifampicin, desacetylrifampicin and isoniazid during combined therapy. Journal of Antimicrobial Chemotherapy 5: 447–454 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Nair, K.G.S.; Epstein, I.G.; Baron, H. and Mulinos, M.G.: Absorption, distribution and excretion of cycloserine in man, a new antibiotic, following oral administration. Antibiotic Medicine 1: 72–80 (1956).

    Google Scholar 

  • Nakao, M.: Studies on the metabolism of para-aminosalicylic acid. I. Paper chromatographic analysis of human urine. Journal of Biochemistry 44: 327–335 (1957).

    CAS  Google Scholar 

  • Niemisto, M.: The influence of sustained release effect on cycloserine concentration in serum. Scandinavian Journal of Respiratory Disease 71: 4–7 (1970).

    Google Scholar 

  • Nitti, V.; Virgilio, R.; Patricolo, M.R. and Iuliano, A.: Pharmacokinetic study of intravenous rifampicin. Chemotherapy 23: 1–6 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Novi, C.; Bissoli, F.; Simonati, V.; Volpini, T.; Baroli, A. and Vignati, G.: Rifampicin and digoxin: Possible drug interaction in a dialysis patient. Journal of the American Medical Association 244: 2521–2522 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Ochs, H.R.; Greenblatt, D.J.; Roberts, G.M. and Dengler, H.J.: Diazepam interaction with antituberculosis drugs. Clinical Pharmacology and Therapeutics 29: 671 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Offe, H.A.; Siefkin, W. and Domagk, G.: The tuberculostatic activity of hydrazine derivatives from pyridine carboxylic acids and carbonyl compounds. Zeitschrift für Naturforschung 7B: 462–472 (1952).

    CAS  Google Scholar 

  • Ogg, C.; Toseland, P. and Cameron, J.: Pulmonary tuberculosis in a patient on intermittent hemodialysis. British Medical Journal 2: 283–284 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Olsen, W.A.; Dayton, P.G.; Israili, Z.H. and Pruitt, A.W.: Spectrophotofluorometric assay for isoniazid and acetylisoniazid in plasma adapted to pediatric studies. Clinical Chemistry 23: 745–748 (1977).

    Google Scholar 

  • Olsen, W.A.; Pruitt, A.W.; Hall, C. and Dayton, P.G.: Pharmacokinetics of isoniazid in children. Pharmacologist 18: 153 (1976).

    Google Scholar 

  • Organick, A.B. and Wilson, E.M.: Multiple drugs in retreatment of chronic pulmonary tuberculosis. Diseases of the Chest 53: 73–83 (1968).

    Article  Google Scholar 

  • Orme, B.M. and Cutler, R.E.: The relationship between kanamycin pharmacokinetics: Distribution and renal function. Clinical Pharmacology and Therapeutics 10: 543–550 (1969).

    PubMed  CAS  Google Scholar 

  • Otten, H.; Plempel, M. and Siegenthaler, W.: Reaction of isoniazid with antiacids and food; in Antibioticka Fiebel, pp. 598–610 (George Thieme, Stuttgart 1975).

    Google Scholar 

  • Pawlowska, I. and Pniewsk, T.: Studies on the pharmacokinetics of rifampicin in the body of patients with pulmonary tuberculosis. Arzneimittel-Forschung 29: 1906–2001 (1979).

    PubMed  CAS  Google Scholar 

  • Peets, E.A.; Sweeney, W.M.; Placc, V.A. and Buyske, D.A.: The absorption, excretion and metabolic fate of ethambutol in man. American Review of Respiratory Disease 88: 51–58 (1964).

    Google Scholar 

  • Pentikainen, P.J.; Wan, S.H. and Azarnoff, D.L.: Bioavailability of aminosalicylic acid and its various salts in humans. IV. Comparison of four brands of sodium salts. Journal of Pharmaceutical Sciences 63: 1431–1434 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Perry, W.: Calcium metabolism during rifampicin and isoniazid therapy. Tubercle 64: 58–58 (1983).

    Article  Google Scholar 

  • Pessayre, D.; Bentala, M.; Degott, C.; Nouel, C.; Miguet, J.P.; Rueff, B. and Benhamou, J.P.: Isoniazid-rifampicin fulminant hepatitis. A possible consequence on the enhancement of isoniazid hepatotoxicity by enzyme induction. Gastroenterology 72: 284–289 (1977).

    PubMed  CAS  Google Scholar 

  • Peters, J.H.; Gordon, G.R.; Murray, J.F.; Ichikawa, W.; Gelber, R.H.; Welch, T.M. and Goucher, C.R.: Measurement of rifampin in plasma: Chemical versus bacteriological assay. Proceedings of the Western Pharmacological Society 20: 211–215 (1977).

    CAS  Google Scholar 

  • Pilheu, J.A.; De Salvo, M.C. and Koch, O.R.: Effects of antituberculosis regimens containing isoniazid and rifampicin on the liver. A light and electron microscopic study. American Review of Respiratory Disease 119: 407–412 (1979).

    Google Scholar 

  • Pissiotis, C.A.; Nichols, R.L. and Condon, R.E.: Absorption and excretion of intraperitoneally administered kanamycin sulfate. Surgery, Gynecology and Obstetrics 134: 995–998 (1972).

    PubMed  CAS  Google Scholar 

  • Pitre, D.; Facino, R.M.; Carini, M. and Carlo, A.: In vitro biotransformation of pyrazinamide by rat liver: Identification of a new metabolite. Pharmacological Research Communications 13: 351–362 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Place, V.A.; Peets, E.A.; Buyske, D.A. and Little, R.R.: Metabolic and special studies of ethambutol in normal volunteers and tuberculosis patients. Annals of the New York Academy of Sciences 135: 775–781 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Place, V.A. and Thomas, J.P.: Clinical pharmacology of ethambutol. American Review of Respiratory Disease 87: 901–904 (1963).

    PubMed  CAS  Google Scholar 

  • Polasa, K. and Krishnaswamy, K.: Effect of food on bioavailability of rifampicin. Journal of Clinical Pharmacology 23: 433–437 (1983).

    PubMed  CAS  Google Scholar 

  • Polk, R.E.; Tenenbaum, M. and Kline, B.: Isoniazid and ethambutol absorption with jejunoileal bypass. Annals of Internal Medicine 89: 430–431 (1981).

    Google Scholar 

  • Poor, D.M.; Self, T.H. and Davis, H.L.: Interaction of rifampicin and digitoxin. Archives of Internal Medicine 143: 599 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Prasad, J.S. and Krishnaswamy, K.: Streptomycin pharmacokinetics in malnutrition. Chemotherapy 24: 333–337 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Pyle, M.M.: Ethambutol and viomycin. Medical Clinics of North America 54: 1317–1327 (1970).

    PubMed  CAS  Google Scholar 

  • Raghupati, G.; Kailasam, S.; Nair, N.G.K.; Narayana, A.S.L. and Tripathy, S.P.: Effect of prednisolone and rifampicin on isoniazid metabolism in slow and rapid inactivators of isoniazid. Antimicrobial Agents and Chemotherapy 18: 661–666 (1980).

    Article  Google Scholar 

  • Rao, K.V.N.; Kailasam, S.; Menon, N.K. and Radharriahna, S.: Inactivation of isoniazid by condensation in a syrup preparation. Indian Journal of Medical Science 50: 1343–1353 (1981).

    Google Scholar 

  • Ratti, B.; Toselli, A.; Beretta, E. and Bernareggi, A.: HPLC assay of pyrazinoic acid in human plasma in the presence of pyrazinamide and other antituberculosis drugs using automatic sampler. Farmaco-Edizione Scientifica 37: 226–234 (1982).

    CAS  Google Scholar 

  • Reidenberg, M.; Shear, L. and Cohen, R.: Elimination of isoniazid in patients with impaired renal function. American Review of Respiratory Disease 108: 1426–1428 (1973).

    PubMed  CAS  Google Scholar 

  • Remmer, H.: Induction of drug metabolizing enzyme system in the liver. European Journal of Clinical Pharmacology 5: 116–120 (1972).

    Article  CAS  Google Scholar 

  • Roboz, J.; Suzuki, R. and Yu, T.F.: Mass fragmentographic determination of pyrazinamide and its metabolites in serum and urine. Journal of Chromatography 147: 337–347 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Robson, J.M. and Sullivan, F.M.: Antituberculosis drugs. Pharmacological Reviews 15: 169–223 (1963).

    PubMed  CAS  Google Scholar 

  • Russell, D.W.: Permeability of human erythrocytes to isonicotinic acid hydrazide and its metabolites. Canadian Journal of Physiology and Pharmacology 51: 230–233 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Sarma, G.R.; Kailasam, S.; Nair, N.G.K.; Narayana, A.S.L. and Tripathy, S.P.: Effect of prednisolone and rifampicin on isoniazid metabolism in slow and rapid inactivators of isoniazid. Antimicrobial Agents and Chemotherapy 18: 661–666 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Schirmer, R.E.; Kleber, J.W. and Black, H.R.: Correlation of dissolution, disintegration and bioavailability of aminosalicylic acid tablets. Journal of Pharmaceutical Sciences 62: 1270–1273 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Self, T.H. and Morris, T.: Interaction of rifampicin and chlorpropamide. Chest 77: 800–801 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Sen, P.K.; Chatterjee, R. and Saha, J.R.: Thiacetazone and isoniazid in tuberculosis. Journal of the Indian Medical Association 61: 306–308 (1973).

    PubMed  CAS  Google Scholar 

  • Sen, P.K.; Chatterjee, J.R.; Saha, J.R. and Roy, H.S.: Thiacetazone concentrations in blood related to grouping of tubercular patients, its treatment results and toxicity. Journal of the Indian Medical Association 62: 557–564 (1974).

    CAS  Google Scholar 

  • Shohet, J.S.: An improved method for the colorimetric assay of thiacetazone in pharmaceutical preparations. Analyst 99: 755–758 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Siegler, D.I.; Burley, D.M.; Bryant, M.; Citron, K.M. and Standen, S.M.: Effects of meals on rifampicin absorption. Lancet 2: 197–198 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Snider, Jr, D.E. and Powell, K.E.: Should women taking antituberculosis drugs breast feed. Archives of Internal Medicine 144: 589–590 (1984).

    Article  PubMed  Google Scholar 

  • Spector, R. and Lorenzo, W.V.: The active transport of para-aminosalicylic acid from the cerebrospinal fluid. Journal of Pharmacology and Experimental Therapeutics 185: 642–648 (1973).

    PubMed  CAS  Google Scholar 

  • Stottmeier, K.D.; Beam, R.E. and Kubica, G.P.: The determination of drug susceptibility of mycobacteria by pyrazinamide in 7HIO agar. American Review of Respiratory Disease 96: 1072–1077 (1966).

    Google Scholar 

  • Stottmeier, K.D.; Beam, R.E. and Kubica, G.P.: The absorption and excretion of pyrazinamide. Preliminary studies in laboratory animals and man. American Review of Respiratory Disease 98: 70–74 (1968).

    PubMed  CAS  Google Scholar 

  • Strauss, I. and Erhardt, F.: Ethambutol absorption, excretion and dosage in patients with renal tuberculosis. Chemotherapy 15: 148–157 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Sutton, G. and Kupferberg, H.J.: Isoniazid as an inhibitor of primidone metabolism. Neurology 25: 1179–1181 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Sved, S.; McGilveray, I.J. and Beaudoin, N.: Bioavailability of three isoniazid formulations. Journal of Pharmaceutical Sciences 66: 1761–1764 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Tiitinen, H.: Isoniazid and ethionamide serum levels and inactivation in Finnish subjects. Scandinavian Journal of Respiratory Disease 50: 110–115 (1969a).

    CAS  Google Scholar 

  • Tiitinen, H.: Modification by para-aminosalicylic acid and sulfamethazine of the isoniazid inactivation in man. Scandinavian Journal of Respiratory Disease50: 281–290 (1969b).

    CAS  Google Scholar 

  • Timbrell, J.A.; Mitchell, J.R.; Snodgrass, W.R. and Nelson, S.D.: Isoniazid hepatotoxicity: The relationship between covalent binding and metabolism in vivo. Journal of Pharmacology and Experimental Therapeutics 213: 364–369 (1980).

    PubMed  CAS  Google Scholar 

  • Timbrell, J.A.; Wright, J.M. and Baillie, T.A.: Monoacetylhydrazine as a metabolite of isoniazid in man. Clinical Pharmacology and Therapeutics 22: 602–608 (1976).

    Google Scholar 

  • Tusum-Barima, Y. and Carruthers, S.G.: Quinidine-rifampicin interaction. New England Journal of Medicine 304: 1466–1469 (1981).

    Article  Google Scholar 

  • Valsalan, V.C. and Cooper, G.L.: Carbamazepine intoxication caused by interaction with isoniazid. British Medical Journal 285: 261–262 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Venho, V.M.K. and Koskinen, R.: The effect of pyrazinamide, rifampicin and clycoserine on the blood levels and urinary excretion of isoniazid. Annals of Clinical Research 3: 277–280 (1971).

    PubMed  CAS  Google Scholar 

  • Waksman, S.A. (Ed.): The Literature on Streptomycin, 1944–1952. (Rutgers University Press, New Brunswick 1952).

    Google Scholar 

  • Wan, S.H.; Pentikainen, P.J. and Azarnoff, D.L.: Bioavailability of aminosalicylic acid and its various salts in humans. III. Absorption from tablets. Journal of Pharmaceutical Sciences 63: 711–798 (1974).

    Google Scholar 

  • Way, E.L.; Perry, O.; Allawald, C. and Daniels, T.C.: The metabolism of para-aminosalicylic acid in man. Journal of the American Pharmaceutical Association 44: 65–69(1993).

    Article  Google Scholar 

  • Way, L.E.; Smith, P.K.; Howie, D.L.; Weiss, R. and Swanson, R.: The absorption, distribution, excretion and fate of para-aminosalicylic acid. Journal of Pharmacology and Experimental Therapeutics 93: 368–382 (1948).

    PubMed  CAS  Google Scholar 

  • Weber, W.W. and Hein, D.W.: Clinical pharmacokinetics of isoniazid. Clinical Pharmacokinetics 4: 401–422 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Weber, W.W.; Hein, D.W.; Litwin, A. and Lower Jr, G.M.: Relationship of acetylator status to isoniazid toxicity, lupus erythematosus, and bladder cancer. Federation Proceedings 42: 3080–3097 (1983).

    Google Scholar 

  • Weiner, I.M. and Tinker, J.P.: Pharmacology of pyrazinamide: Metabolic and renal function studies related to the mechanism of drug-induced urate retention. Journal of Pharmacology and Experimental Therapeutics 180: 411–434 (1972).

    PubMed  CAS  Google Scholar 

  • Wright, J.M.; Stokes, E.F. and Sweeney, V.P.: Isoniazid induced carbamazepine toxicity and vice versa. New England Journal of Medicine 307: 1325–1327 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Youmans, G.P.: Tuberculosis (W.B. Saunders, Philadelphia 1979).

    Google Scholar 

  • Yoshimura, H.; Itoh, O. and Yonezawa, S.: Microbiological and thin layer chromatographic identification of aminoglycoside antibiotics in animal bodes. Japanese Journal of Veterinarian Science 44: 233–239 (1982).

    Article  CAS  Google Scholar 

  • Yu, T.F.; Perel, J.; Berger, L.; Roboz, J.; Israili, Z.H. and Dayton, P.G.: The effect of the interaction of pyrazinamide and probenecid on the urinary uric acid excretion in man. American Journal of Medicine 63: 723–727 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Zilly, W.; Breimer, D.D. and Richter, E.: Pharmacokinetic interactions with rifampicin. Clinical Pharmacokinetics 2: 61–70 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Zitkova, L. and Tousek, J.: Pharmacokinetics of cycloserine and terizidone. Chemotherapy 20: 18–28 (1974).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Holdiness, M.R. Clinical Pharmacokinetics of the Antituberculosis Drugs. Clin Pharmacokinet 9, 511–544 (1984). https://doi.org/10.2165/00003088-198409060-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198409060-00003

Keywords

Navigation