Abstract
The pharmacokinetic properties of estazolam, a triazolo benzodiazepine hypnotic agent, were assessed in a series of healthy volunteers following single and multiple doses. After single oral doses of 2–16 mg, peak plasma concentrations were reached within 6 h. Values of elimination half-life ranged from 8.3–31.2 h (mean 17.0 h) and did not vary significantly with dose. During 3 weeks of therapy, steady-state plasma concentrations increased approximately in proportion to increasing doses, and accumulation was essentially complete within 3 days of each dose change. The mean observed accumulation ratio was 1.84, which was slightly larger than the predicted ratio of 1.53. Exposure to multiple-dose estazolam therapy had no significant influence on the kinetics of a single dose of antipyrine, suggesting that estazolam neither stimulates nor inhibits enzyme activity in humans. Thus the accumulation and elimination kinetics of estazolam can be classified as intermediate to those of the short-acting (such as oxazepam) and the long-acting (such as diazepam) benzodiazepine derivatives.
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References
Boxenbaum, H. G., Riegelman, S., Elashoff, R. M.: Statistiscal estimations in pharmacokinetics. J. Pharmacokinet. Biopharm. 2, 123–148 (1974)
Brodie, B. B., Axelrod, J., Soberman, R., Levy, B. B.: The estimation of antipyrine in biological materials. J. Biol. Chem. 179, 25–29 (1949)
de Silva, J. A. F., Puglisi, C. V.: Determination of medazepam (Nobrium), diazepam (Valium) and their major biotransformation products in blood and urine by electron capture gasliquid chromatography. Anal. Chem. 42, 1725–1736 (1970)
Gibaldi, M., Perrier, D.: Pharmacokinetics. New York: Marcel Dekker 1975
Greenblatt, D. J.: Determination of desmethyldiazepam in plasma by electron-capture GLC: Application to pharmacokinetic studies of clorazepate. J. Pharm. Sci. 67, 427–429 (1978a)
Greenblatt, D. J.: Simultaneous gas chromatographic analysis of diazepam and its major metabolite desmethyldiazepam, with use of double internal standardization. Clin. Chem. 24, 1838–1841 (1978b)
Greenblatt, D. J.: Predicting steady-state serum concentrations of drugs. Annu. Rev. Pharmacol. Toxicol. 19, 347–356 (1979)
Greenblatt, D. J., Koch-Weser, J.: Clinical pharmacokinetics. New Engl. J. Med. 293, 702–705, 964–970 (1975)
Greenblatt, D. J., Locniskar, A.: Spectrophotometric assay of antipyrine in plasma: a reevaluation. Int. J. Clin. Pharmacol. Biopharm. (in press, 1979)
Greenblatt, D. J., Shader, R. I.: Benzodiazepines in clinical practice. New York: Raven 1974
Greenblatt, D. J., Shader, R. I.: Pharmacokinetic understanding of antianxiety drug therapy. South. Med. J. 71 (Suppl. 2), 2–9 (1978)
Greenblatt, D. J., Allen, M. D., MacLaughlin, D. S., Huffman, D. H., Harmatz, J. S., Shader, R. I.: Single- and multiple-dose kinetics of oral lorazepam in humans: The predictability of accumulation. J. Pharmacokinet. Biopharm. 7, 159–179 (1979a)
Greenblatt, D. J., Franke, K., Shader, R. I.: Analysis of lorazepam and its glucuronide metabolite by electron-capture gas-liquid chromatography: Use in pharmacokinetic studies of lorazepam. J. Chromatogr. 146, 311–320 (1978)
Greenblatt, D. J., Pfeifer, H. J., Ochs, H. R., Franke, K., MacLaughlin, D. S., Smith, T. W., Koch-Weser, J.: Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration. J. Pharmacol. Exp. Ther. 202, 365–378 (1977)
Greenblatt, D. J., Shader, R. I., Franke, K., MacLaughlin, D. S., Harmatz, J. S., Allen, M. D., Werner, A., Woo, E.: Pharmacokinetics and bioavailability of intraveous, intramuscular and oral lorazepam in humans. J. Pharm. Sci. 68, 57–63 (1979b)
Isozaki, H., Tanaka, M., Inanaga, K.: Effect of a triazolobenzodiazepine derivative, estazolam, on all-night sleep pattern. Curr. Ther. Res. 20, 493–509 (1976)
Kanai, Y.: The biotransformation of 8-chloro-6-phenyl-4H-s-triazolo [4,3,-a] [1,4] benzodiazepine (D-40TA), a new central depressant, in man, dog and rat. Xenobiotica 4, 441–456 (1974)
Loo, J. C. K., Riegelman, S.: Assessment of pharmacokinetic constants from postinfusion blood curves obtained after IV infusion. J. Pharm. Sci. 59, 53–55 (1970)
Marquardt, D. W.: An algorithm for least-squares estimation of non-linear parameters. J. Soc. Ind. Appl. Math. 11, 431–441 (1963)
Momose, T., Ishii, S., Kuge, T.: Controlled comparison of estazolam and nitrazepam as hypnotics on the preoperative night sleep. Curr. Ther. Res. 19, 277–291 (1976)
Usanis, R. A.: NLIN-Nonlinear least-squares estimation of parameters. Library Services Series No. LSR-089-1. North Carolina: Triangle Universities Computation Center 1972
Vesell, E. S., Passananti, G. T., Viau, J.-P., Epps, J. E., DiCarlo, F. J.: Effects of chronic prazepam administration on drug metabolism in man and rat. Pharmacology 7, 179–206 (1972)
Wagner, J. G.: Fundamentals of clinical pharmacokinetics Illinois: Drug Intelligence 1975
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Allen, M.D., Greenblatt, D.J. & Arnold, J.D. Single- and multiple-dose kinetics of estazolam, a triazolo benzodiazepine. Psychopharmacology 66, 267–274 (1979). https://doi.org/10.1007/BF00428318
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DOI: https://doi.org/10.1007/BF00428318