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Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers

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Abstract

Our objective was to evaluate a possible pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers. The study consisted of two periods: Period 1 (reference), when each volunteer received a single dose of 5 mg zolpidem and Period 2 (test), when each volunteer received a single dose of 5 mg zolpidem and 500 mg ciprofloxacin. Between the two periods, the subjects were treated for 5 days with a single daily dose of 500 mg ciprofloxacin. Plasma concentrations of zolpidem were determined during a 12-hour period following drug administration. Pharmacokinetic parameters of zolpidem administered in each treatment period were calculated using non-compartmental analysis and the data from two periods were compared to determine statistically significant differences. In the two periods of treatments, the mean peak plasma concentrations (C max) were 75.73 ± 28.34 ng/ml (zolpidem alone) and 80.58 ± 22.40 ng/ml (zolpidem after pre-treatment with ciprofloxacin). The t max, times taken to reach C max, were 0.91 ± 0.42 and 1.44 ± 0.61 h, respectively, and the total areas under the curve (AUC0–∞) were 300.2 ± 115.5 and 438.1 ± 142.6 ng h/ml, respectively. The half-life of zolpidem was 2.39 ± 0.53 h when administered alone and 3.34 ± 0.87 h after pre-treatment with ciprofloxacin. These differences were statistically significant for C max, t max, AUC0–∞, half-life and mean residence time. Ciprofloxacin interacts with zolpidem in healthy volunteers, raising its bioavailability by about 46%. This magnitude of effect is likely to be clinically significant.

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References

  • Abou-Auda HS, Mustafa AA, Al-Humayyd MS (2008) Pharmacokinetic interaction of ketoconazole and itraconazole with ciprofloxacin. Biopharm Drug Dispos 29(1):29–35

    Article  CAS  PubMed  Google Scholar 

  • Cysneiros RM, Farkas D, Harmatz JS, Von Moltke LL, Greenblatt DJ (2007) Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Clin Pharmacol Ther 82(1):54–62. doi:10.1038/sj.clpt.6100211

    Article  CAS  PubMed  Google Scholar 

  • Farkas D, Volak LP, Harmatz JS, Von Moltke LL, Court MH, Greenblatt DJ (2009) Short-term clarithromycin administration impairs clearance and enhances pharmacodynamic effects of trazodone but not of zolpidem. Clin Pharmacol Ther 85(6):644–650. doi:10.1038/clpt.2008.293

    Article  CAS  PubMed  Google Scholar 

  • Herrlin K, Segerdahl M, Gustafsson LL, Kalso E (2000) Methadone, ciprofloxacin and adverse drug reactions. Lancet 356(9247):2069–2070

    Article  CAS  PubMed  Google Scholar 

  • Iqbal Z, Khan A, Naz A, Khan JA, Khan GS (2009) Pharmacokinetic interaction of ciprofloxacin with diclofenac: a single-dose, two-period crossover study in healthy adult volunteers. Clin Drug Investig 29(4):275–281

    Article  CAS  PubMed  Google Scholar 

  • Lamba JK, Lin YS, Schuetz EG, Thummel KE (2002) Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 54:1271–1294. doi:10.1016/S0169-409X(02)00066-2

    Article  CAS  PubMed  Google Scholar 

  • Neve EPA, Ingelman-Sundberg M (2010) Cytochrome P450 proteins: retention and distribution from the endoplasmic reticulum. Curr Opin Drug Discov Devel 13(1):78–85

    CAS  PubMed  Google Scholar 

  • Saari TI, Laine K, Leino K, Valtonen M, Neuvonen PJ, Olkkola KT (2006) Effect of voriconazole on the pharmacokinetics and pharmacodynamics of zolpidem in healthy subjects. Br J Clin Pharmacol 63(1):116–120. doi:10.1111/j.1365-2125.2006.02707.x

    Article  PubMed  Google Scholar 

  • Salvà P, Costa J (1995) Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet 29(3):142–153

    Article  PubMed  Google Scholar 

  • Schuirmann DJ (1987) A comparison of the 2 one-sided tests procedure and the power approach for assessing the equivalence of average bioavailability. J Pharmacokinet Biopharm 15:657–680

    Article  CAS  PubMed  Google Scholar 

  • Swainston HT, Keatin GM (2005) Zolpidem: a review of its use in the management of insomnia. CNS Drugs 19(1):65–89

    Article  Google Scholar 

  • The European Agency for the Evaluation of Medicinal Products, Committee for medicinal products for human use (2010) Guideline on the investigation of bioequivalence. http://www.ema.europa.eu/pdfs/human/qwp/140198enrev1fin.pdf. Accessed 31 May 2010

  • U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (2002) Guidance for Industry. Bioavailability and Bioequivalence studies for orally administered drug products-general considerations. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070124.pdf. Accessed 31 May 2010

  • Villikka K, Kivistö KT, Luurila H, Neuvonen PJ (1997) Rifampin reduces plasma concentrations and effects of zolpidem. Clin Pharmacol Ther 62(6):629–634. doi:10.1016/S0009-9236(97)90082-5

    Article  CAS  PubMed  Google Scholar 

  • Von Moltke LL, Greenblatt DJ, Granda BW, Duan SX, Grassi JM, Venkatakrishnan K (1999) Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. Br J Clin Pharmacol 48:89–97. doi:10.1046/j.1365-2125.1999.00953.x

    Article  Google Scholar 

Download references

Acknowledgments

This work was supported by a PNII-IDEI project, code 462, contract 229/2007 financed by The National University Research Council Romania, for which the authors gratefully acknowledge.

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Correspondence to Laurian Vlase.

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Vlase, L., Popa, A., Neag, M. et al. Pharmacokinetic interaction between zolpidem and ciprofloxacin in healthy volunteers. Eur J Drug Metab Pharmacokinet 35, 83–87 (2011). https://doi.org/10.1007/s13318-010-0014-9

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  • DOI: https://doi.org/10.1007/s13318-010-0014-9

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