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

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 (t1/2) of 1.40 h. The mean clearance (CL) and the apparent volume of distribution (VdB) of 1,5-DCQA were 0.44 l/h/kg and 0.89 l/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.