Effect of genetic polymorphisms of SLC28A1, ABCG2, and ABCC4 on bioavailability of mizoribine in healthy Japanese males

Drug Metab Pharmacokinet. 2011;26(5):538-43. doi: 10.2133/dmpk.dmpk-11-nt-040. Epub 2011 Jul 5.

Abstract

The aim of the present study was to investigate the genetic factors responsible for the interindividual variability in the bioavailability of mizoribine. Thirty healthy Japanese men aged 20-49 years and weighing 53-75 kg participated in the present study and took 150 mg of mizoribine. Urine samples were collected periodically for 12 h after the dose, and the bioavailability of mizoribine was calculated from the estimated total urinary excretion from time zero to infinity. The bioavailability of mizoribine in the 30 subjects ranged from 60.3% to 99.4%. The mean bioavailability of mizoribine in subjects with the concentrative nucleoside transporter 1 (SLC28A1) 565-A/A allele (75.4%) was significantly lower than that in subjects with the SLC28A1 565-G/G allele (90.1%). On the other hand, the bioavailability of mizoribine was not affected by polymorphisms of breast cancer resistance protein (ABCG2) C421A and multidrug resistance-associated protein 4 (ABCC4) G2269A. The findings in the present prospective study suggested that the genetic test for the SLC28A1 G565A polymorphism is promising for predicting the Japanese subjects with lower bioavailability of mizoribine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Asian Continental Ancestry Group / genetics
  • Biological Availability
  • Humans
  • IMP Dehydrogenase / antagonists & inhibitors
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / urine
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Neoplasm Proteins / genetics*
  • Polymorphism, Genetic
  • Prospective Studies
  • Ribonucleosides / pharmacokinetics*
  • Ribonucleosides / urine

Substances

  • ABCC4 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Immunosuppressive Agents
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Ribonucleosides
  • cif nucleoside transporter
  • mizoribine
  • IMP Dehydrogenase