NDLI: Effect of CYP3A4*1G, CYP3A5*3, POR*28, and ABCB1 C3435T on the pharmacokinetics of nifedipine in healthy Chinese volunteers.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Wang, Xiao-Fei Yan, Liang Cao, Hui-Min Wei, Lu-Man Yang, Wei-Hong Zhang, Sheng-Jun Zhang, Li-Rong
Abstract	OBJECTIVE: Nifedipine is a calcium channel blocker that is widely used in the treatment of cardiovascular disease. However, significant individual variances in the disposition of nifedipine have been reported, and genetic factors are considered to play an important role. The aim of the present study was to investigate the effect of CYP3A41G, CYP3A53, ABCB1-C3435T, and POR28 genetic polymorphisms on nifedipine pharmacokinetics in healthy Chinese volunteers. METHODS: 45 healthy Chinese volunteers enrolled in this study received a single oral dose of 90 mg nifedipine after providing written informed consent. Volunteers were genotyped for CYP3A41G, CYP3A53, POR28, and ABCB1-C3435T. The blood concentrations of nifedipine were determined by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method. RESULTS AND DISCUSSION: There were significant differences of AUC00-∞ and AUC0-48h in the different CYP3A53 genotype groups (p = 0.043 and p = 0.048, respectively). The CYP3A53 GG group and POR28 CT/TT group were found to have lower AUC00-∞ and Cmax compared with the POR28 CC group (p = 0.046 and p = 0.002, respectively). In addition, the POR28 CT/TT group was found to have longer t1/2 but lower Cmax than the CYP3A41G GG group (p = 0.032 and p = 0.002, respectively) as well as the CYP3A41G GG and the CYP3A53 GG group (p = 0.038 and p = 0.036, respectively) compared with the POR28 CC group. No significant associations were found between CYP3A41G/ABCB1-C3435T polymorphism and pharmacokinetics of nifedipine. CONCLUSION: Both CYP3A53 and POR28 polymorphisms are found to be associated with the difference in disposition of nifedipine; POR*28 is considered to have an impact on CYP3A4 activity.
File Format	HTM / HTML
ISSN	09461965
Issue Number	9
Volume Number	53
Journal	Int. Journal of Clinical Pharmacology and Therapeutics
Language	English
Publisher	Dustri-Verlag
Publisher Date	2015-09-01
Publisher Place	Germany
Access Restriction	Subscribed
Subject Keyword	Discipline Pharmacology Calcium Channel Blockers Pharmacokinetics Cytochrome P-450 Cyp3a Genetics Nadph-ferrihemoprotein Reductase Nifedipine Adult Female Genotype Humans Male P-glycoproteins Young Adult Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

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