Pharmacokinetics and metabolism of 1,5-dicaffeoylquinic acid in rats following a single intravenous administration

J Pharm Biomed Anal. 2006 Feb 13;40(2):417-22. doi: 10.1016/j.jpba.2005.06.037. Epub 2005 Sep 6.

Abstract

1,5-Dicaffeoylquinic acid (1,5-DCQA) is a potentially important HIV-1 integrase inhibitor widely distributed in many plants. To characterize the pharmacokinetic and metabolic properties of 1,5-DCQA in rats following single intravenous administration (160 mg/kg), the plasma concentrations of 1,5-DCQA were measured by high-performance liquid chromatography (HPLC) and the metabolites formed in urine were identified by liquid chromatography-mass spectrometry (LC-MS) in parallel to diode-array detection (DAD). The results showed that the concentrations of 1,5-DCQA in plasma declined rapidly in a biphasic manner with a mean terminal half-life (t(1/2)) of 1.40 h. The mean clearance (CL) and the apparent volume of distribution (Vd(B)) of 1,5-DCQA were 0.44l/h/kg and 0.89l/kg, respectively. A total of 15 metabolites in rat urine were identified, including four isomeric O-mono-methylated (M1-M4), six isomeric O-di-methylated (M5-M10), one isomeric O-mono-methyl-glucuronidated (M11) and four isomeric O-di-methyl-glucuronidated (M12-M15) metabolites. The O-methylation positions of three important metabolites (M1, M2 and M5) were determined (3''-, 3'-, and 3',3''-) by comparing with synthesized standards. These results suggested that the disappearance of 1,5-DCQA from plasma was rapid, and that its quick urinary excretion and extensive metabolism, including methylation and glucuronidation, were two factors causing its rapid elimination from the circulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods
  • Cinnamates / pharmacokinetics*
  • Cinnamates / urine
  • Glucuronides / urine
  • HIV Integrase Inhibitors / pharmacokinetics*
  • HIV Integrase Inhibitors / urine
  • Injections, Intravenous
  • Male
  • Mass Spectrometry
  • Methylation
  • Rats
  • Rats, Wistar
  • Reproducibility of Results

Substances

  • Cinnamates
  • Glucuronides
  • HIV Integrase Inhibitors
  • cynarine