Drug Res (Stuttg) 2013; 63(12): 633-638
DOI: 10.1055/s-0033-1349889
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics and Bioequivalence Evaluation of Leflunomide Tablets in Korean Healthy Volunteers

Y.-J. Lim
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
,
E.-J. Shim
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
2   Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea
,
H.-S. Kim
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
2   Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea
,
M. Oh
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
,
J.-H. Shon
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
2   Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea
,
J.-G. Shin
1   Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Republic of Korea
2   Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea
,
B.-S. Moon
3   CJ CHEILJEDANG Corp., Seoul, Republic of Korea
,
G.-S. Song
3   CJ CHEILJEDANG Corp., Seoul, Republic of Korea
,
E.-Y. Kim
2   Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Republic of Korea
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Weitere Informationen

Publikationsverlauf

received 17. April 2013

accepted 28. Juni 2013

Publikationsdatum:
24. Juli 2013 (online)

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.

 
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