title: 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 AUCt and the Cmax after administration of leflunomide tablets. Bioequivalence was defined as the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of AUCt and Cmax for the test and reference drugs being within the range of 0.80-1.25. The GMRs (90% CI) for AUCt and Cmax 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 AUCt and Cmax 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.
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Lim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: E-J
authors.initials: EJ
authors.lastname: Shim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: M
authors.initials: M
authors.lastname: Oh
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Shon
authors.affiliation: Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea.
authors.forename: J-G
authors.initials: JG
authors.lastname: Shin
authors.affiliation: CJ CHEILJEDANG Corp., Seoul, Republic of Korea.
authors.forename: B-S
authors.initials: BS
authors.lastname: Moon
authors.affiliation: CJ CHEILJEDANG Corp., Seoul, Republic of Korea.
authors.forename: G-S
authors.initials: GS
authors.lastname: Song
authors.affiliation: Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea.
authors.forename: E-Y
authors.initials: EY
authors.lastname: Kim
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003437:Crotonates / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006885:Hydroxybutyrates; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077339:Leflunomide; D008875:Middle Aged; D009570:Nitriles; D056910:Republic of Korea; D013810:Therapeutic Equivalency; D014052:Toluidines / Q000097:blood*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D003437:Crotonates; D006885:Hydroxybutyrates; D007555:Isoxazoles; D009570:Nitriles; D014052:Toluidines; C527525:teriflunomide; D000077339:Leflunomide