کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2478831 1113406 2014 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development of a Pharmacokinetic Interaction Model for Co-administration of Simvastatin and Amlodipine
ترجمه فارسی عنوان
توسعه یک مدل تعامل فارماکوکینتیک برای همکاری با سیمواستاتین و آملودیپین
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی

Summary:A model for drug interaction between amlodipine and simvastatin was developed using concentration data obtained from a multiple-dose study consisting of single- and co-administration of amlodipine and simvastatin conducted in healthy Koreans. Amlodipine concentrations were assumed to influence the clearance of simvastatin and simvastatin acid, which as well as the oral bioavailability was allowed to vary depending on genetic polymorphisms of metabolic enzymes. Covariate effects on drug concentrations were also considered. The developed model yielded a 46% increase in simvastatin bioavailability and a 13% decrease in simvastatin clearance when amlodipine 10 mg was co-administered. When CYP3A4/5 polymorphisms were assessed by a mixture model, extensive metabolizers yielded a decrease in simvastatin bioavailability of 81% and a decrease in simvastatin clearance by 4.6 times as compared to poor metabolizers. Sixty percent of the usual dose was the optimal simvastatin dose that can minimize the interaction with amlodipine 10 mg. Age and weight had significant effects on amlodipine concentrations. In conclusion, this study has quantitatively described the pharmacokinetic interaction between simvastatin and amlodipine using a modeling approach. Given that the two drugs are often prescribed together, the developed model is expected to contribute to more efficient and safer drug treatment when they are co-administered.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Metabolism and Pharmacokinetics - Volume 29, Issue 2, 2014, Pages 120-128