Comparative pharmacokinetics study of two different clindamycin capsule formulations: a randomized, two-period, two-sequence, two-way crossover clinical trial in healthy volunteers

Abstract

The comparative pharmacokinetic (PK) study of two brands of clindamycin hydrochloride (CAS 21462-39-5) was carried out on 32 healthy Indian subjects in an open label randomized, two way crossover, two period, two sequence, two treatment trial with a minimum washout period of 7 days. Plasma samples were collected at 10 min interval for the 1^st hour, at 1 h interval for the next 6 h, at 2 h interval for next 12 h and finally at the 24^th hour (pre-dose as baseline value) after drug administration. The concentrations of clindamycin in plasma were determined using high performance liquid chromatography (HPLC) technique with UV detector [lower limit of quantitation (LLOQ) 0.05 μg · mL⁻¹). All PK parameters were calculated from data on clindamycin content in plasma using a non-compartmental model. Primary PK parameters were maximum plasma concentration (C_max), area under the curve from zero to t^th hour (AUCT) and area under the curve from zero to infinite (AUCI), whereas secondary PK parameters were elimination half-life (t_halt), elimination rate constant (K_el) and time to reach maximum plasma concentration (T_max). All primary PK parameters (log transformed) were subjected to ANOVA analysis and two one-sided Student’s t-test (TOST) to construct the 90% confidence intervals. The result of ANOVA showed that all primary PK parameters at 90% confident intervals were within the limit of 80–125%. All the values such as 95.7–109.00% for C_max( 99.5–117% for AUCT and 99.1% to 114% for AUCI showed pharmacokinetic equivalence and indicated that this comparative pharmacokinetic study was well designed to conclude that the test formulation and reference formulation were pharmaco-kinetically equivalent and hence bioequi-valent with respect to rate and extent of absorption.

Key words

Bioequivalence - Clindamycin - Macrolide antibiotic - Pharmacokinetics

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