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 (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.
Yang
B
B
Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.
Meng
Z Y
ZY
Yan
L P
LP
Dong
J X
JX
Zou
L B
LB
Tang
Z M
ZM
Dou
G F
GF
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002934:Cinnamates / Q000493:pharmacokinetics* / Q000652:urine; D020719:Glucuronides / Q000652:urine; D019428:HIV Integrase Inhibitors / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D008745:Methylation; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
D002934:Cinnamates; D020719:Glucuronides; D019428:HIV Integrase Inhibitors; C100257:cynarine