Bioequivalence evaluation of two marketed brands of stavudine 40 mg capsules in healthy human South African volunteers

Stavudine (d4T), a thymidine nucleoside analogue has been effectively used for treatment of patients infected with HIV. A randomized, two-way, crossover study was conducted in 24 fasting, healthy, Caucasian male volunteers to compare plasma pharmacokinetic (PK) profile and single-dose tolerability of a new d4T formulation (Stavir ®, Cipla Ltd, India; 40 mg capsule, test, T) with that of reference (R) formulation (Zerit ®, Bristol-Myers Squib, NJ, USA; capsule, 40 mg). Each volunteer received T and R formulation separated by at least 10 days of drug free wash-out period. Plasma concentrations of d4T, determined upto 24 h post-dose by a validated LC-MS/MS assay were utilized to assess PK parameters such as maximum observed plasma concentration ( C max), time to C max ( t max), and area under plasma concentration curve (AUC ∞). The primary plasma PK parameters, C max, and AUC ∞, of anti-retroviral were comparable for either of the formulations. t max was achieved within an hour suggesting rapid absorption of d4T from both formulations. Geometric mean ratios (GMR) (percentage reference) of AUC ∞ and C max, and their 90% confidence intervals (CI) were 106.32 [102.52–110.26] and 102.32 [90.25–116.00], respectively. As the 90% CI of GMR were entirely within 80–125% for log-transformed parameters, two formulations were considered bioequivalent, in the extent and rate of absorption. Both formulations exhibited similar tolerability under fasting conditions.