Enhanced bioavailability of etoposide after oral or intravenous administration of etoposide with kaempferol in rats

Arch Pharm Res. 2009 Jan;32(1):133-8. doi: 10.1007/s12272-009-1127-z. Epub 2009 Jan 29.

Abstract

This study was to investigate the effect of kaempferol on the pharmacokinetics of etoposide after oral or intravenous administration of etoposide in rats. The oral (6 mg/kg) or intravenous (2 mg/kg) etoposide was administered to rats alone or 30 min after the oral kaempferol (1, 4, or 12 mg/kg) administration. Compared to the oral control group, the presence of kaempferol significantly (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) increased the area under the plasma concentrationtime curve (AUC) and the peak concentration (C(max)) of the oral etoposide. Kaempferol decreased significantly (4 or 12 mg/kg, P < 0.05) the total body clearance (CL/F) of oral etoposide, while there was no significant change in the terminal halflife (t(1/2)), the elimination rate constant (K(el)) and the time to reach the peak concentration (T(max)) of etoposide in the presense of kaempferol. Consequently, the absolute bioavailability (AB%) of oral etoposide with kaempferol was significantly higher (4 mg/kg, P < 0.05; 12 mg/kg, P < 0.01) than those from the control group. Compared to the intravenous control group, the presence of kaempferol enhanced the AUC of intravenously administered etoposide, however, only presence of 12 mg/kg of kaempferol significant (P < 0.05) increased AUC of etoposide. The enhanced bioavailability of oral etoposide by kaempferol could have been due to an inhibition of cytochrom P450 (CYP) 3A and P-glycoprotein (P-gp) in the intestinal or decreased total body clearance in the liver by kaempferol. The dosage regimen of etoposide should be taken into consideration for potential drug interaction when combined with kaempferol or dietary supplements containing kaempferol in patients.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Biological Availability
  • Cytochrome P-450 CYP3A / metabolism
  • Cytochrome P-450 CYP3A Inhibitors
  • Dietary Supplements*
  • Drug Interactions
  • Etoposide / administration & dosage*
  • Etoposide / pharmacokinetics*
  • Injections, Intravenous
  • Intestines / drug effects
  • Intestines / enzymology
  • Kaempferols / administration & dosage*
  • Liver / drug effects
  • Liver / enzymology
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Cytochrome P-450 CYP3A Inhibitors
  • Kaempferols
  • Etoposide
  • kaempferol
  • Cytochrome P-450 CYP3A