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논문 기본 정보

자료유형
학술저널
저자정보
Hwang Sejung (Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine Seoul Korea.Kidney Research Institute Seoul National University Medical Research Center Seoul Korea.) Lee Soyoung (Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine Seoul Korea.Kidney Research Institute Seoul National University Medical Research Center Seoul Korea.) Yoon Jangsoo (Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine Seoul Korea.) Chung Jae-Yong (Department of Clinical Pharmacology and Therapeutics Seoul National University College of Medicine Seoul Korea.Integrated Major in Innovative Medical Science Seoul National University Graduate School)
저널정보
대한의학회 Journal of Korean Medical Science Journal of Korean Medical Science Vol.38 No.22
발행연도
2023.6
수록면
1 - 13 (13page)
DOI
10.3346/jkms.2023.38.e173

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Background: Carvedilol is a beta-adrenergic receptor antagonist primarily metabolized by cytochromes P450 (CYP) 2D6. This study established a carvedilol population pharmacokinetic (PK)–pharmacodynamic (PD) model to describe the effects of CYP2D6 genetic polymorphisms on the inter-individual variability of PK and PD. Methods: The PK–PD model was developed from a clinical study conducted on 21 healthy subjects divided into three CYP2D6 phenotype groups, with six subjects in the extensive metabolizer (EM, *1/*1, *1/*2), seven in the intermediate metabolizer-1 (IM-1, *1/*10, *2/*10), and eight in the intermediate metabolizer-2 (IM-2, *10/*10) groups. The PK–PD model was sequentially developed, and the isoproterenol-induced heart rate changes were used to establish the PD model. A direct effect response and inhibitory Emax model were used to develop a carvedilol PK–PD model. Results: The carvedilol PK was well described by a two-compartment model with zeroorder absorption, lag time, and first-order elimination. The carvedilol clearance in the CYP2D6*10/*10 group decreased by 32.8% compared with the other groups. The inhibitory concentration of carvedilol estimated from the final PK–PD model was 16.5 ng/mL regardless of the CYP2D6 phenotype. Conclusion: The PK–PD model revealed that the CYP2D6 genetic polymorphisms were contributed to the inter-individual variability of carvedilol PK, but not PD.

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