Enhanced oral exposure of diltiazem by the concomitant use of naringin in rats

Int J Pharm. 2005 Nov 23;305(1-2):122-8. doi: 10.1016/j.ijpharm.2005.09.004. Epub 2005 Oct 13.

Abstract

The present study aims to investigate the effect of naringin, a flavonoid, on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats following an oral administration of diltiazem (15 mgkg(-1)) to rats in the presence and absence of naringin (5 and 15 mgkg(-1)). Compared to the control given diltiazem alone, the C(max) and AUC of diltiazem increased by twofolds in rats pretreated with naringin, while there was no significant change in T(max) and terminal plasma half-life (T(1/2)) of diltiazem. Consequently, absolute and relative bioavailability values of diltiazem in the presence of naringin were significantly higher (p<0.05) than those from the control group. Metabolite-parent AUC ratio in the presence of naringin decreased by 30% compared to the control group, implying that naringin could be effective to inhibit the metabolism of diltiazem. In conclusion, the concomitant use of naringin significantly enhanced the oral exposure of diltiazem in rats.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • Animals
  • Area Under Curve
  • Biological Availability
  • Calcium Channel Blockers / blood
  • Calcium Channel Blockers / pharmacokinetics*
  • Cytochrome P-450 Enzyme Inhibitors
  • Diltiazem / analogs & derivatives*
  • Diltiazem / blood
  • Diltiazem / pharmacokinetics*
  • Drug Interactions
  • Flavanones / administration & dosage
  • Flavanones / pharmacology*
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Calcium Channel Blockers
  • Cytochrome P-450 Enzyme Inhibitors
  • Flavanones
  • deacetyldiltiazem
  • Diltiazem
  • naringin