Development of a Pharmacokinetic Interaction Model for Co-administration of Simvastatin and Amlodipine

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 c...

Full description

Saved in:
Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2014, Vol.29 (2), p.120-128
Main Authors: Son, Hankil, Lee, Donghwan, Lim, Lay Ahyoung, Jang, Seong Bok, Roh, Hyerang, Park, Kyungsoo
Format: Article
Language:eng ; jpn
Subjects:
Administration, Oral
Adult
Age Factors
amlodipine
Amlodipine - administration & dosage
Amlodipine - blood
Amlodipine - pharmacokinetics
Biological Availability
Body Weight
Calcium Channel Blockers - administration & dosage
Calcium Channel Blockers - blood
Calcium Channel Blockers - pharmacokinetics
Cross-Over Studies
Cytochrome P-450 CYP3A - genetics
Cytochrome P-450 CYP3A - metabolism
Drug Interactions
drug-drug interaction
Genotype
Healthy Volunteers
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics
Male
metabolite
Middle Aged
mixture model
Models, Biological
Phenotype
Polymorphism, Genetic
Polypharmacy
population anlyisis
Republic of Korea
simvastatin
Simvastatin - administration & dosage
Simvastatin - blood
Simvastatin - pharmacokinetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
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.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.DMPK-13-RG-053