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Heritability of metformin renal clearance
Author(s) -
Leabman M.,
Brown C.,
Chung J.,
Castro R.,
Swan G. E.,
Lin E.,
Giacomini K. M.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.123
Subject(s) - heritability , metformin , twin study , renal function , coefficient of variation , urine , clearance , drug , medicine , renal physiology , endocrinology , pharmacology , chemistry , urology , biology , diabetes mellitus , genetics , chromatography
Background Twin studies have been used to determine the genetic contribution to variation in hepatic drug metabolism. In contrast, little is known about the contribution of genetic factors to variation in renal drug elimination. In this study, we used monozygotic twin pairs to assess the heritability of the clearance of the anti‐diabetic agent, metformin, a drug that is eliminated exclusively in the kidneys. Methods We administered 850 mg metformin to six monozygotic twin pairs and collected plasma and urine samples over 24 hours. Concentrations of metformin were determined by LC‐MS. A modified calculation was used for assessing the heritability (H) of renal clearance: H= (V between pairs − V within pairs )/V between pairs, where V is variance. Results In this interim analysis, we observed that 95% of the variation in renal clearance of metformin could be attributed to genetic factors (H=0.95), with an overall correlation coefficient of 0.97. Conclusions While the formal heritability calculation will require the enrollment of dizygotic twin pairs, this initial finding indicates that genetic factors contribute substantially to the renal clearance of metformin. The degree of heritability in renal clearance is similar to that observed in classical twin studies of drugs that are eliminated by hepatic metabolism. Clinical Pharmacology & Therapeutics (2005) 77 , P61–P61; doi: 10.1016/j.clpt.2004.12.123