Influence of capsaicin on fluctuation of digoxin pharmacokinetics in lipopolysaccharide-treated rats

Xenobiotica. 2012 Aug;42(8):798-807. doi: 10.3109/00498254.2012.663514. Epub 2012 Mar 14.

Abstract

In the present study, we investigated the influence of Cap on digoxin pharmacokinetics in lipopolysaccharide (LPS)-treated rats. After the oral administration of digoxin (0.1 mg/kg), the area under the plasma concentration-time curve (AUC) of digoxin increased significantly until day 3 after LPS treatment. In the LPS + Cap group, the recovery period of AUC was shortened to 3 days. On days 5 and 7, the maximum plasma concentrations decreased significantly as compared to the control group. The bioavailability of digoxin in LPS group was higher than that in the LPS + Cap group. The hepatic cytochrome P450 (CYP) 3A2 content decreased significantly until day 5 after LPS administration, but it returned to the control level until 5 days in the LPS + Cap group. Hepatic CYP3A2 mRNA expression of LPS group decreased significantly until day 3, but it returned to the control level on day 3 and increased significantly until day 7 in the LPS + Cap group. The DNA-binding activity of pregnane X receptor (PXR) was increased on days 3-7 in the Cap and LPS + Cap group. Cap decreased the absorption of digoxin by inducing CYP3A2 mRNA expression via indirect activation of PXR in LPS-treated rats.

MeSH terms

  • Administration, Oral
  • Animals
  • Blotting, Western
  • Capsaicin / administration & dosage
  • Capsaicin / pharmacology*
  • Cytochrome P-450 CYP3A
  • DNA / metabolism
  • Digoxin / administration & dosage
  • Digoxin / pharmacokinetics*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation / drug effects
  • Injections, Intravenous
  • Lipopolysaccharides / administration & dosage
  • Lipopolysaccharides / pharmacology*
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Pregnane X Receptor
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, Steroid / metabolism

Substances

  • Lipopolysaccharides
  • Pregnane X Receptor
  • RNA, Messenger
  • Receptors, Steroid
  • Digoxin
  • DNA
  • Cytochrome P-450 CYP3A
  • Capsaicin