Pharmacokinetics and Bioequivalence Evaluation of Leflunomide Tablets in Korean Healthy Volunteers

Abstract

Leflunomide is a disease-modifying antirheumatic drug. The purpose of this study was to evaluate the bioequivalence of a test drug (CJ leflunomide) and a commercially available reference drug (Arava^®) at 2 doses (10 and 20 mg) in healthy Korean volunteers. This was a single-dose (28 individuals enrolled at each dose group), randomized, open-label, 2-way crossover study. The 2 treatment periods were separated by a 56-day wash-out interval. Blood sampling was conducted until 672 h after drug administration. Plasma teriflunomide (active metabolite of leflunomide) concentrations were determined, and pharmacokinetic parameters were calculated. Bioequivalence was evaluated using an ANOVA model, based on the AUC_t and the C_max after administration of leflunomide tablets. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUC_t and C_max for the test and reference drugs being within the range of 0.80–1.25. The GMRs (90% CI) for AUC_t and C_max were 0.9506 (0.9091–0.9941) and 0.9861 (0.9360–1.0389), respectively, in the 10 mg study, and 0.9524 (0.9101–0.9968) and 0.9740 (0.9314–1.0186), respectively, in the 20 mg study. The 90% CIs of AUC_t and C_max at each dose were within the accepted range for bioequivalence. Based on the results, the test drug (CJ leflunomide) was bioequivalent to the commercially available reference drug (Arava^®) at both doses.

Key words

leflunomide - teriflunomide - bioequivalence - pharmacokinetics - safety

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