Effect of P-glycoprotein inhibitors erythromycin and cyclosporin A on brain pharmacokinetics of nimodipine in rats

Eur J Drug Metab Pharmacokinet. Oct-Dec 2003;28(4):309-13. doi: 10.1007/BF03220184.

Abstract

Effect of P-glycoprotein (P-gp) inhibitors erythromycin (Ery) and cyclosporin A(CsA) on brain pharmacokinetics of nimodipine (NMD) in rats was studied. NMD concentrations in rat plasma and brain were determined after iv 2 mg/kg NMD alone, co-administration with Ery and CsA, respectively. It was found that concentrations of NMD in plasma of the three groups had a little difference, but brain concentrations of NMD in rats co-administrated with Ery and CsA were significantly higher than those in rats NMD alone. Significances of NMD in rat brain were found at 20, 40, 60 and 90 min after iv NMD. The brain T(1/2) in rat treated with ery(75.0 min) and CsA(79.0 min) were larger than that (44.2 min) in rats NMD alone. The results indicated that P-gp inhibitors Ery and CsA may increase concentration in rat brain by inhibiting elimination of NMD from brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Area Under Curve
  • Brain / metabolism*
  • Calcium Channel Blockers / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Cyclosporine / pharmacology*
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Erythromycin / pharmacology*
  • Half-Life
  • Kidney / metabolism
  • Male
  • Nimodipine / pharmacokinetics*
  • Rats
  • Testis / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Bacterial Agents
  • Calcium Channel Blockers
  • Enzyme Inhibitors
  • Nimodipine
  • Erythromycin
  • Cyclosporine