Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans

A single dose, randomized, open-label, two-way crossover study

Ji-Young Park, K. A. Kim, Y. H. Lee, S. W. Park, G. H. Lee, J. H. Ryu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 AUC0-t and Cmax 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 AUC0-t, AUC0-∞, and Cmax 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.

Original languageEnglish
Pages (from-to)291-295
Number of pages5
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume48
Issue number4
DOIs
Publication statusPublished - 2010 Jan 1

Fingerprint

leflunomide
Therapeutic Equivalency
Cross-Over Studies
A 771726
Pharmacokinetics
Healthy Volunteers
Antirheumatic Agents
Methotrexate
Pharmaceutical Preparations
Rheumatoid Arthritis

Keywords

  • A77 1726
  • Bioavailability
  • Bioequivalence
  • Leflunomide
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Pharmacokinetic comparison and bioequivalence of two leflunomide formulations in humans : A single dose, randomized, open-label, two-way crossover study. / Park, Ji-Young; Kim, K. A.; Lee, Y. H.; Park, S. W.; Lee, G. H.; Ryu, J. H.

In: International Journal of Clinical Pharmacology and Therapeutics, Vol. 48, No. 4, 01.01.2010, p. 291-295.

Research output: Contribution to journalArticle

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abstract = "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 AUC0-t and Cmax 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 AUC0-t, AUC0-∞, and Cmax 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.",
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N2 - 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 AUC0-t and Cmax 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 AUC0-t, AUC0-∞, and Cmax 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.

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