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Bioequivalence of the pharmacokinetics between tofacitinib aspartate and tofacitinib citrate in healthy subjects

Translational and Clinical Pharmacology 2020년 28권 3호 p.160 ~ 167
Shin Won-Suk, 양아영, 윤현지, 조두연, 박경희, 신현주, 김언혜,
소속 상세정보
 ( Shin Won-Suk ) - CHA University School of Medicine CHA Bundang Medical Center Department of Clinical Pharmacology and Therapeutics
양아영 ( Yang A-Young ) - CHA University School of Medicine CHA Bundang Medical Center Department of Clinical Pharmacology and Therapeutics
윤현지 ( Yun Hyeon-Ji ) - CHA University School of Medicine CHA Bundang Medical Center Department of Clinical Pharmacology and Therapeutics
조두연 ( Cho Doo-Yeoun ) - CHA University School of Medicine CHA Bundang Medical Center Department of Clinical Pharmacology and Therapeutics
박경희 ( Park Kyung-Hee ) - Daewoong Pharmaceutical Co. Ltd.
신현주 ( Shin Hyun-Ju ) - Daewoong Pharmaceutical Co. Ltd.
김언혜 ( Kim An-Hye ) - CHA University School of Medicine CHA Bundang Medical Center Department of Clinical Pharmacology and Therapeutics

Abstract


Tofacitinib is an oral disease-modifying anti-rheumatic drug to selectively inhibit Janus kinases. Tofacitinib is a representative small molecule inhibitor that is used to treat many diseases including rheumatoid arthritis and various autoimmune conditions. Unlike biological agents, tofacitinib has several advantages, including the ability to be administered orally and a short half-life. This study aimed to evaluate the bioequivalence of the pharmacokinetics (PK) between tofacitinib aspartate 7.13 mg (test formulation) and tofacitinib citrate 8.08 mg (reference formulation; Xeljanz®) in healthy subjects. A randomized, open-label, single-dose, 2-sequence, 2-period, 2-treatment crossover trial was conducted in 41 healthy volunteers. A total of 5 mg of tofacitinib as the test or the reference formulation was administered, and serial blood samples were collected up to 14 hours after dosing for PK analyses. The plasma concentration of tofacitinib was determined by ultra-performance liquid chromatography-tandem mass spectrometry. A non-compartmental analysis was used to estimate the PK parameters. A total of 35 subjects completed the study and the study drug was well-tolerated. The mean maximum concentration (Cmax) and area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) for the test formulation were 52.67 ng/mL and 133.86 ng?h/mL, respectively, and 50.61 ng/mL and 133.49 h?ng/mL for the reference formulation, respectively. The geometric mean ratios (90% confidence intervals) of the Cmax and AUClast between the 2 formulations were 1.041 (0.944?1.148) and 1.003 (0.968?1.039), respectively. Tofacitinib aspartate exhibited bioequivalent PK profiles to those of the reference formulation.

키워드

Bioequivalence; Pharmacokinetics; Tofacitinib

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