Bioequivalence of indinavir capsules in healthy volunteers

ABSTRACT

Asian Biomedicine Vol. 4 No. 1 February 2010; 95-101 Original article Bioequivalence of indinavir capsules in healthy volunteers Suvatna Chulavatnatola, Kumthorn Malathumb, Sasisopin Kiertiburanakulb, Kittisak Sriphac, Pojawon Lawanprasertd aDepartment of Pharmacy, Faculty of Pharmacy, bDepartment of Medicine, Faculty of Medicine, Ramathibodi Hospital, cDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, dDepartment of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand 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 2x400 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.