Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans: A single dose, randomized, open-label, two-way crossover study

Background and aims: Leflunomide is a disease-modifying antirheumatic drug (DMARD) with comparable efficacy to methotrexate in the treatment of rheumatoid arthritis. We compared the pharmacokinetic characteristics of two leflunomide formulations in healthy subjects and assessed whether these formulations were bioequivalent. Subjects and methods: A randomized, two-way, crossover study was conducted in 24 healthy male volunteers to compare the pharmacokinetics of two leflunomide formulations after administration of a single 20 mg dose of each drug with a 7 week washout period. Blood samples for the analysis of A77 1726, the main active metabolite of leflunomide, were obtained 624 h after drug administration. Results: After administering a single dose of 20 mg of each leflunomide formulation, the mean AUC_0-t and C_max values of A771726 were 487.3 ± 167.6 μg*h/ml and 2.24 ± 0.85 μg/ml for the reference formulation and 468.5 ± 148.6 μg*h/ml and 1.98 ± 0.45 μg/ml for the test formulation, respectively. The 90% confidence intervals of the test/reference mean ratios for AUC_0-t, AUC_0-∞, and C_max fell within the predetermined equivalence range of 0.8 - 1.25. No serious adverse events occurred during the study period. Conclusions: The two leflunomide formulations showed similar pharmacokinetic profiles in terms of A77 1726, and the test formulation was found to be bioequivalent to the reference formulation with respect to the rate and extent of leflunomide absorption.