Bioequivalence of indinavir capsules in healthy volunteers

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Background: Indinavir, one component in the HAART regimen, plays an important role in the current treatment of HIV-infection and AIDS. Availability and accessibility of qualified generic indinavir to patients may be the keys for the success of treatment. Objective: Compare the rate and extent of absorption of a generic indinavir formulation with those of an original formulation in healthy Thai volunteers. Method: A randomized, two-period, two-treatment, two-sequence, crossover study with a two-week washout period was performed. A single dose of 2×400 mg indinavir capsules of each formulation was administered to 24 volunteers after an overnight fast. Indinavir plasma concentrations up to 10 hours postdose were determined using high-performance liquid chromatography. Relevant pharmacokinetic parameters were derived and tested for statistically significant differences using ANOVA and criteria of bioequivalence determination were applied. Results: No statistically significant differences were demonstrated for pharmacokinetic parameters including Cmax, Tmax, AUC0-t, and AUC0-∞ derived from the two formulations (n=23, p>0.05). The criteria of bioequivalence determination i.e., the 90% confidence intervals on the mean ratio (generic/original formulation) of natural logarithmtransformed values of Cmax, AUC0-t and AUC0-∞ were 86.3-106.5%, 94.0-108.5%, and 93.9-108.5%, respectively. Conclusion: As the mean ratios of Cmax, AUC0-t and AUC0-∞ of the generic and original formulations were entirely within the guideline range of bioequivalence (80.0-125.0%), the two formulations were considered bioequivalent in terms of rate and extent of absorption.

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  • 1. Wainberg MA. Generic HIV drugs-enlightened policy for global health. N Engl J Med. 2005; 352:747-50.

  • 2. Bartlett JA Muro EP. Generic and branded drugs for the treatment of people living with HIV/AIDS. J Int Assoc Physicians AIDS Care. 2007; 6:15-23.

  • 3. Hugen PWH Burger DM ter Hofstede HJM Koopmans PP Hekster YA. Development of an indinavir oral liquid for children. Am J Health Syst Pharm. 2000; 57:1332-9.

  • 4. Yeh KC Deutsch PJ Haddix H Hesney M Hoagland V Ju WD et al. Single-dose pharmacokinetics of indinavir and the effect of food. Antimicrob Agents Chemother. 1998; 42:332-8.

  • 5. Hsu A Granneman GR Cao G Carothers L Japour A El-Shourbagy T et al. Pharmacokinetic interaction between ritonavir and indinavir in healthy volunteers. Antimicrob Agents Chemother. 1998; 42:2784-91.

  • 6. The United States Pharmacopoeial Convention Inc. The United States Pharmacopeia 26 / National Formulary 21. Rockville USA; 2003.

  • 7. Drug Control Division. Thailand Guidelines for the Conduct of Bioavailability and Bioequivalence Studies. Bangkok Thailand: Food and Drug Administration Ministry of Public Health; 2000.

  • 8. Poirier JM Robidou P Jaillon P. Determination of indinavir in plasma by solid-phase extraction and column liquid chromatography. Ther Drug Monit. 1999; 21:404-10.

  • 9. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) Center for Veterinary Medicine (CVM). Guidance for Industry Bioanalytical Method Validation. Available from: 2001/[2 June 2005].

  • 10. Wonnacott RJ Wonnacott TH editors. Econometrics. New York:John Wiley & Sons 1970; p. 132.

  • 11. Association of Southeast Asian Nations (ASEAN) Consultative Committee for Standards and Quality- Pharmaceutical Product Working Group. Guidelines for the Conduct of Bioavailability and Bioequivalence Studies. 2004.

  • 12. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry. Statistical Approaches to Establishing Bioequivalence. January 2001.

  • 13. Kraft WK McCrea JB Winchell GA Carides A Lowry R Woolf EJ et al. Indinavir and rifabutin drug interactions in healthy volunteers. J Clin Pharmacol. 2004; 44:305-13.

  • 14. Burger D Boyd M Duncombe C Felderhof M Mahanontharit A Ruxrungtham K et al. Pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in HIV-infected Thai patients. J Antimicrob Chemother. 2003; 51:1231-8.

  • 15. Schiffman SS Zervakis J Heffron S Heald AE. Effect of protease inhibitors on the sense of taste. Nutrition. 1999; 15:767-72.

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