Pharmacokinetics and Comparative Bioavailability of Two Terbinafine Hydrochloride Formulations after Single-dose Administration in Chinese Healthy Subjects

Abstract

The bioavailability of a new terbinafine (CAS 91161-71-6) preparation was compared with a commercially available original preparation (reference) of the drug in 19 Chinese healthy male volunteers. The study was performed in an open, randomized, single blind two-sequence, two-period crossover design. Under fasting conditions, each subject received a single oral dose of 250 mg terbinafine as a test or reference formulation with a 7-day washout period between the two preparations. The plasma concentrations of terbinafine were analyzed by a sensitive liquid chromatography-ultraviolet spectrometry method. The pharmacokinetic parameters included AUC_0-τ, AUC_0-∞, C_max, t_1/2, and T_max. The values of AUC_0–t demonstrated nearly identical bioavailability of terbinafine from the examined formulations. The AUC_0–48 of terbinafine was 5982.85 ± 2449.17 and 6761.63 ± 3140.33 ng · h/ml for the test and reference formulation, respectively. The maximum plasma concentration (C_max) of terbinafine was 1656.25 ± 623.18 ng/ml for the test and 1552.07 ± 660.35 ng/ml for the reference product, respectively. No statistical differences were observed for C_max and the area under the plasma concentrationtime curve for terbinafine. The 90% confidence limits calculated for C_max and AUC from zero to infinity (AUC_0–∞) of terbinafine were within the bioequivalence range (80%– 125% for AUC). This study shows that the test formulation is bioequivalent to the reference formulation of terbinafine.

Key words

Antifungal - CAS 91161-71-6 - Terbinafine, bioequivalence, pharmacokinetics

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