Contribution of polymorphisms in UDP-glucuronosyltransferase and CYP2D6 to the individual variation in disposition of carvedilol

Yoh Takekuma, Toru Takenaka, Masami Kiyokawa, Koujiro Yamazaki, Hiroshi Okamoto, Akira Kitabatake, Hiroyuki Tsutsui, Mitsuru Sugawara

研究成果: ジャーナルへの寄稿学術誌査読

34 被引用数 (Scopus)

抄録

Purpose. It has been reported that carvedilol, which has beta-adrenergic blocking and vasodilating activities, is mainly metabolized by UDP-glucuronosyltransferase (UGT) 1A1, UGT2B4, UGT2B7 and CYP2D6. The aim of this study was to determine whether the activity of glucuronidation has an influence on the area under the curve (AUC) of carvedilol and whether polymorphisms in UGTs and CYP2D6 contribute to individual variation in disposition of carvedilol in Japanese. Methods. Plasma concentrations of carvedilol and its glucuronide were determined by reversed-phase high-performance liquid chromatography (HPLC). Genotyping of UGT1A1, UGT2B4 and UGT2B7 genes was carried out by the direct sequence method. CYP2D6 genotyping was carried out using an amplification refractory mutation system (ARMS) assay and PCR-restriction fragment length polymorphism (RFLP). Results. The level of carvedilol glucuronidation ability in the high-level AUC group was significantly lower than that in the low-level group. The frequencies of UGT1A1*6, UGT2B7*3 and CYP2D6*10 in the low level ability of glucuronidation group were significantly higher than those in the high level group, and the same tendency was found in the frequency of CYP2D6*5, though there was no significant difference. Conclusion. Polymorphisms of UGT1A1, UGT2B7 and CYP2D6 strongly affect the pharmacokinetics and disposition of carvedilol in Japanese.

本文言語英語
ページ(範囲)101-112
ページ数12
ジャーナルJournal of Pharmacy and Pharmaceutical Sciences
9
1
出版ステータス出版済み - 3月 1 2006
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学

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