Prediction of systemic exposure to cyclosporine in Japanese pediatric patients

J Hum Genet. 2006;51(11):969-976. doi: 10.1007/s10038-006-0048-7. Epub 2006 Sep 14.

Abstract

The monitoring of the blood concentration at 2 h (C(2)) after the oral administration of a cyclosporine (CsA) microemulsion was reconfirmed to be useful for the prediction of systemic exposure, the area under the blood concentration-time curve from 0 to 4 h (AUC(0-4)), in a group of Japanese patients, consisting of 33 children aged 5-15 years and 19 young adults aged 16-27 years, with a greater correlation for C(2) (r = 0.927) than the trough concentration (r = 0.488). The dose-normalized AUC(0-4) was independent of gender or indications for CsA, while it depended on body size, i.e., the age (P = 0.065) and total body weight (P = 0.026). MDR1 C3435T had a weak, but insignificant effect (P = 0.072); it was about 22-31% lower in the patients with TT(3435). Co-administration of a steroid and further treatment with nifedipine had a more intensive effect (P = 0.018); co-administration resulted in a 51% increase in the dose-normalized AUC(0-4). A strong effect was also observed for the serum total cholesterol level (P = 0.001). Collectively, the discrepancies in the results on MDR1 C3435T among investigators might be due to variability in the age/total body weight, co-administration drugs or serum lipid level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Area Under Curve
  • Child
  • Child, Preschool
  • Cyclosporine / pharmacokinetics*
  • Drug Monitoring
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacokinetics*
  • Japan
  • Male
  • Time Factors

Substances

  • Immunosuppressive Agents
  • Cyclosporine