Effect of genetic variation in the organic cation transporter 2 on the renal elimination of metformin.
Pharmacogenet Genomics
; 19(7): 497-504, 2009 Jul.
Article
en En
| MEDLINE
| ID: mdl-19483665
OBJECTIVE: The goal of this study was to determine the effect of a genetic variant in the organic cation transporter 2 (OCT2), OCT2-808G/T, which results in an amino acid change, A270S, on the pharmacokinetics of the antidiabetic drug, metformin. METHODS: The uptake of metformin was performed in stably transfected HEK-293 cells expressing the empty vector (MOCK), the reference OCT2-808G, and the variant OCT2-808T. Healthy individuals with known OCT2 genotypes [14 homozygous for the OCT2 reference allele (808G/G) and nine heterozygous for the variant allele (808G/T, *3D)] were recruited to this study. Metformin concentrations in plasma and urine were measured by liquid chromatography-tandem mass spectrometry method. Creatinine levels were also measured in plasma and urine. Pharmacokinetic parameters were evaluated for both the groups. RESULTS: We observed that in HEK-293 stably transfected cells, OCT2-808T had a greater capacity to transport metformin than did the reference OCT2. Metformin pharmacokinetics was characterized in 23 healthy volunteers of Caucasian and African-American ancestries. We observed that the renal clearance (CL(R)) and the net secretion (SrCL(R)) of metformin were significantly different between the volunteers heterozygous for the variant allele (808G/T), and the volunteers homozygous for the reference allele (808G/G) (P<0.005). Multivariate analysis revealed that OCT2 genotype was a significant predictor of CL(R) and SrCL(R) of metformin (P<0.01). CONCLUSION: We conclude that genetic variation in OCT2 plays an important role in the CL(R) and SrCL(R) of metformin in healthy volunteers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polimorfismo de Nucleótido Simple
/
Proteínas de Transporte de Catión Orgánico
/
Riñón
/
Metformina
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Pharmacogenet Genomics
Asunto de la revista:
FARMACOLOGIA
/
GENETICA MEDICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos