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Effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide

Archives of Pharmacal Research 2020년 43권 11호 p.1207 ~ 1213
배정우, 오경열, 윤소정, 신효빈, 정의현, 조창근, 임창우, 강푸름, 최창익, 장춘곤, 이석용, 이윤정,
소속 상세정보
배정우 ( Bae Jung-Woo ) - Sungkyunkwan University School of Pharmacy
오경열 ( Oh Kyung-Yul ) - Sungkyunkwan University School of Pharmacy
윤소정 ( Yoon So-Jung ) - Sungkyunkwan University School of Pharmacy
신효빈 ( Shin Hyo-Bin ) - Sungkyunkwan University School of Pharmacy
정의현 ( Jung Eui-Hyun ) - Sungkyunkwan University School of Pharmacy
조창근 ( Cho Chang-Keun ) - Sungkyunkwan University School of Pharmacy
임창우 ( Lim Chang-Woo ) - Sungkyunkwan University School of Pharmacy
강푸름 ( Kang Pu-Reum ) - Sungkyunkwan University School of Pharmacy
최창익 ( Choi Chang-Ik ) - Dongguk University College of Pharmacy
장춘곤 ( Jang Choon-Gon ) - Sungkyunkwan University School of Pharmacy
이석용 ( Lee Seok-Yong ) - Sungkyunkwan University School of Pharmacy
이윤정 ( Lee Yun-Jeong ) - Dankook University College of Pharmacy

Abstract


Metoclopramide inhibits the central and peripheral D2 receptors and is frequently prescribed in adults and children as an antiemetic or a prokinetic drug to control symptoms of upper gastrointestinal motor disorders. Metoclopramide is predominantly metabolized via N-dealkylation and it is primarily mediated by CYP2D6 which is highly polymorphic. Thus, the effects of CYP2D6 genetic polymorphism on the pharmacokinetics of metoclopramide were evaluated in this study. All volunteers were genotyped for CYP2D6 and divided into four different genotype groups (CYP2D6*wt/*wt [*wt = *1 or *2], CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10). Each subject received a single oral dose of metoclopramide 10 mg. Plasma concentrations of metoclopramide were measured by using HPLC-UV. Compared to CYP2D6*wt/*wt, AUCinf of CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 significantly increased by 1.5-, 2.3-, and 2.5-fold, respectively. Cmax also increased significantly in comparison to CYP2D6*wt/*wt across all genotype groups, with 1.5-, 1.7-, and 1.7-fold increases seen in CYP2D6*wt/*10, CYP2D6*10/*10, and CYP2D6*5/*10 groups, respectively. The CL/F of metoclopramide decreased in CYP2D6 genotype groups with decreased function alleles, as decreases of 37%, 56% and 61% were observed in CYP2D6*wt/10, *10/10, and *5/*10 genotype groups in comparison to the CYP2D6*wt/*wt group. In conclusion, the genetic polymorphisms of CYP2D6 significantly affected metoclopramide pharmacokinetics.

키워드

Metoclopramide; CYP2D6; Genotype; Genetic polymorphism; Pharmacokinetics

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