The ABCG2 C421A polymorphism does not affect oral nitrofurantoin pharmacokinetics in healthy Chinese male subjects

Br J Clin Pharmacol. 2008 Aug;66(2):233-9. doi: 10.1111/j.1365-2125.2008.03184.x. Epub 2008 Apr 22.


Aims: A number of drugs are substrates or inhibitors of the efflux transporter breast cancer resistance protein (BCRP; ABCG2), which can limit systemic exposure by reducing absorption and/or increasing biliary elimination. The identification of a BCRP-selective clinical probe drug would provide a useful tool to understand the effect of genetic polymorphisms and transporter-based drug interactions on drug pharmacokinetics. The aim of this study was to assess the utility of nitrofurantoin as a clinical probe substrate for BCRP activity by evaluating the impact of genetic variation on nitrofurantoin pharmacokinetics.

Methods: Nitrofurantoin pharmacokinetics were studied in an open-label, single-oral dose (100 mg) study in 36 male Chinese subjects who were pre-screened for ABCG2 421 CC, CA and AA genotypes (n = 12 each). Plasma and urine concentrations of nitrofurantoin were determined by LC/MS/MS and LC/UV respectively. anova was used to compare pharmacokinetic parameters among genotypes.

Results: There were no significant differences in nitrofurantoin pharmacokinetics among the genotypic cohorts. The geometric mean nitrofurantoin plasma AUC((0-infinity)) (95% confidence interval) values were 2.21 (2.00, 2.45), 2.42 (2.11, 2.78) and 2.32 (1.99, 2.70) microg h ml(-1) and half-life values were 0.79 (0.59, 1.0), 0.76 (0.64, 0.89) and 0.72 (0.62, 0.84) h for ABCG2 421 genotypes CC, CA and AA, respectively. The percentage of dose excreted unchanged in the urine was 43, 44 and 39%, respectively.

Conclusions: The ABCG2 C421A polymorphism had no effect on nitrofurantoin plasma and urine pharmacokinetic parameters in healthy Chinese subjects. These results indicate that nitrofurantoin is not a suitable clinical probe substrate for assessing BCRP activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / drug effects
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Administration, Oral
  • Adult
  • Anti-Infective Agents, Urinary / administration & dosage
  • Anti-Infective Agents, Urinary / pharmacokinetics*
  • Asian People / genetics*
  • Biological Transport / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / drug effects
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Nitrofurantoin / administration & dosage
  • Nitrofurantoin / pharmacokinetics*
  • Polymorphism, Genetic / drug effects*
  • Treatment Outcome


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Anti-Infective Agents, Urinary
  • Neoplasm Proteins
  • Nitrofurantoin