Effects of genetic factors on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients

Guo,Chengxian; Pei,Qi; Tan,Hongyi; Huang,Zhijun; Yuan,Hong; Yang,Guoping

doi:10.3892/br.2014.395

March-2015 Volume 3 Issue 2

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March-2015 Volume 3 Issue 2

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Article

Effects of genetic factors on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients

Authors:
- Chengxian Guo
- Qi Pei
- Hongyi Tan
- Zhijun Huang
- Hong Yuan
- Guoping Yang
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Affiliations: Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China, Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410078, P.R. China
Pages: 195-200
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Published online on: December 2, 2014

https://doi.org/10.3892/br.2014.395
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Abstract

The aim of the present study was to explore the effects of common genetic polymorphisms of cytochrome P450 (CYP)3A4, CYP3A5, cytochrome P450 oxidoreductase (POR) and multidrug resistance protein 1 (MDR1) on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients. The mild‑to‑moderate essential hypertension patients were recruited to complete the genotyping of CYP3A4, CYP3A5, POR and MDR1 by sequencing. After a 1‑week placebo washout period, the subjects received 5 mg oral amlodipine daily for 4 weeks. Serial blood samples were collected prior to the last dosing, and 2, 6 and 24 h post‑dosing. Blood pressures were measured prior and subsequent to dosing, and the demographical data were also collected. The blood samples were collected for laboratory testing. The plasma concentrations of amlodipine were determined by high‑performance liquid chromatography/tandem mass spectrometry. A total of 60 patients, including 31 males and 29 females, completed the 4‑week treatment. The plasma concentration of amlodipine in females at each time point was significantly higher compared to males (P<0.05). However, no significant gender differences existed in antihypertensive efficacy. The genetic polymorphisms of MDR1 C3435T had a certain impact on the plasma concentration of amlodipine, but did not affect its antihypertensive efficacy (P>0.05). The genetic polymorphisms of CYP3A4*1G, CYP3A5*3 and POR A503V showed no impact on plasma concentration and efficacy of amlodipine (P>0.05). Gender and MDR1 gene polymorphism may affect the plasma concentration of amlodipine in hypertensive patients. However, there was no impact on the efficacy of amlodipine.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effects of genetic factors on the pharmacokinetics and pharmacodynamics of amlodipine in primary hypertensive patients

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