Influences of Organic Cation Transporter Polymorphisms on the Population Pharmacokinetics of Metformin in Healthy Subjects

This study investigated the effects of genetic polymorphisms in organic cation transporter (OCT) genes, such as OCT1-3, OCTN1, MATE1, and MATE2-K, on metformin pharmacokinetics. Of particular interest was the influence of genetic polymorphisms as covariates on the variability in the population pharm...

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Bibliographic Details
Published in:The AAPS journal 2013-04, Vol.15 (2), p.571-580
Main Authors: Yoon, Hwa, Cho, Hea-Young, Yoo, Hee-Doo, Kim, Se-Mi, Lee, Yong-Bok
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Analysis of Variance
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Chi-Square Distribution
Drug Dosage Calculations
Gene Frequency
Genotype
Half-Life
Humans
Hypoglycemic Agents - administration & dosage
Hypoglycemic Agents - blood
Hypoglycemic Agents - pharmacokinetics
Male
Metabolic Clearance Rate
Metformin - administration & dosage
Metformin - blood
Metformin - pharmacokinetics
Models, Biological
Nonlinear Dynamics
Organic Cation Transport Proteins - genetics
Organic Cation Transport Proteins - metabolism
Organic Cation Transporter 2
Pharmacogenetics
Pharmacology/Toxicology
Pharmacy
Phenotype
Polymorphism, Genetic
Randomized Controlled Trials as Topic
Research Article
Retrospective Studies
Young Adult
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Summary:This study investigated the effects of genetic polymorphisms in organic cation transporter (OCT) genes, such as OCT1-3, OCTN1, MATE1, and MATE2-K, on metformin pharmacokinetics. Of particular interest was the influence of genetic polymorphisms as covariates on the variability in the population pharmacokinetics (PPK) of metformin using nonlinear mixed effects modeling (NONMEM). In a retrospective data analysis, data on subjects from five independent metformin bioequivalence studies that used the same protocol were assembled and compared with 96 healthy control subjects who were administered a single oral 500 mg dose of metformin. Genetic polymorphisms of OCT2-808 G > T and OCTN1-917C > T had a significant ( P   T and OCTN1-917C > T variants on the CL/ F were significant ( P   T genetic polymorphisms, could be useful in titrating the optimal metformin dose.
ISSN:1550-7416
1550-7416
DOI:10.1208/s12248-013-9460-z