Genetic influences on the pharmacokinetics of orally and intravenously administered digoxin as exhibited by monozygotic twins

Clin Pharmacol Ther. 2009 Dec;86(6):605-8. doi: 10.1038/clpt.2009.170. Epub 2009 Sep 23.

Abstract

The expression and function of the drug transporter P-glycoprotein are highly variable. Environmental and genetic factors contribute to this variation. We studied the disposition of digoxin, a frequently used probe drug for P-glycoprotein function in humans, in monozygotic (MZ) twins and found that digoxin pharmacokinetics after oral and intravenous administration are highly correlated within MZ twins, supporting the hypothesis of a robust contribution from genetic variance. Our study suggests that studies involving twins could be more widely applied to elucidate pharmacogenetics.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Adult
  • Deuterium
  • Digoxin / administration & dosage*
  • Digoxin / pharmacokinetics*
  • Female
  • Genetic Variation*
  • Genotype
  • Humans
  • Infusions, Intravenous
  • Male
  • Phenotype
  • Pilot Projects
  • Registries
  • Twins, Monozygotic / genetics*
  • Twins, Monozygotic / metabolism
  • Young Adult

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Digoxin
  • Deuterium