Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Pharmacokinetics and metabolism of 1,5-dicaffeoylquinic acid in rats following a single intravenous administration
Ist Teil von
Journal of pharmaceutical and biomedical analysis, 2006-02, Vol.40 (2), p.417-422
Ort / Verlag
Amsterdam: Elsevier B.V
Erscheinungsjahr
2006
Quelle
MEDLINE
Beschreibungen/Notizen
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 0.44
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.