Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term remission in patients with ulcerative colitis treated with tacrolimus
Article first published online: 19 DEC 2013
© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 29, Issue 1, pages 60–66, January 2014
How to Cite
Hirai, F., Takatsu, N., Yano, Y., Satou, Y., Takahashi, H., Ishikawa, S., Tsurumi, K., Hisabe, T. and Matsui, T. (2014), Impact of CYP3A5 genetic polymorphisms on the pharmacokinetics and short-term remission in patients with ulcerative colitis treated with tacrolimus. Journal of Gastroenterology and Hepatology, 29: 60–66. doi: 10.1111/jgh.12361
- Issue published online: 19 DEC 2013
- Article first published online: 19 DEC 2013
- Accepted manuscript online: 22 AUG 2013 05:22AM EST
- Manuscript Accepted: 28 JUL 2013
- Eisai Co., Ltd
- Mochida Pharmaceutical Co., LTD.
- Glaxo Smith Kline K.K.
- Mitsubishi Tanabe Pharma Corporation.
- Eisai Co., Ltd.
- ulcerative colitis
Background and Aim
The pharmacokinetics of tacrolimus (Tac) differ among individuals, and genetic polymorphisms of cytochrome P-450 (CYP) 3A4, CYP3A5, and ABCB1 are thought to be involved. The aim of this study was to clarify whether these genetic polymorphisms affect the pharmacokinetics of Tac in patients with ulcerative colitis.
The subjects in this study were 45 patients with moderate-to-severe ulcerative colitis who were resistant to other therapies and were treated with Tac. The subjects were tested for genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1, and the relationship between Tac pharmacokinetics and the remission rate was investigated.
Of the 45 subjects, 24 (53.3%) were CYP3A5 expressers (Exp), and 21 (46.7%) were non-expressers (Non-Exp). The trough level and the dose-adjusted trough level on days 2–5 were significantly higher in the Non-Exp group than in the Exp group (10.16 ± 5.84 vs 4.47 ± 2.50 ng/mL, P < 0.0001, 139.36 ± 77.43 vs 61.37 ± 41.55 ng/mL per mg/kg/day, P < 0.0001). The percentage of patients achieving the optimal trough level on days 2–5 was significantly higher in the Non-Exp group than in the Exp group (40.0% vs 4.3%, P = 0.01). This trend was also observed on days 7–10. On multivariate analysis, factors associated with achievement of the optimal trough level were food non-intake and Non-Exp of CYP3A5. The remission rate was significantly higher in the Non-Exp group than in the Exp group (47.6% vs 16.7%, P = 0.046).
CYP3A5 genetic polymorphisms affected the pharmacokinetics of Tac, so that the short-term clinical remission rate was different between Exp and Non-Exp of CYP3A5.