Pharmacokinetics and metabolism of Dihydroquercetin isolated from Larix sibirica Ledeb

The aim of this study was the investigation of the pharmacokinetic processes of Dihydroquercetin isolated from Larix sibirica Ledeb (DHQ; CAS N° 480–18–2, C₁₅H₁₂O₇; 2,3-dihydro-2-(3,4-dihydroxyphenil)-3,5,7-trihydroxyphenil-4H-1-benzopyran-4-on; 3,5,7,3',4'-penta-hydroxyflavon) and identification it metabolites in blood plasma and urine after single intravenous, oral administration (12.5, 50mg/kg) in rats. Blood plasma and urine samples of rats, containing DHQ-glucuronide were underwent enzymatic hydrolysis with purified β-glucuronidase solution (1). Hydrolyzed samples were extracted with diethyl ether from acidic medium. Quantification of DHQ was performed by reverse-phase HPLC with UV- and MS-detection. It was established that DHQ is a short-living drug (the half-elimination time was not exceed of 1.25h). The drug was determined for 6h in rats. Absolute bioavailability is about 24%. 8.30% of DHQ from administered oral dose (250mg/kg) was excreted with daily urine. Analyzed compound was not detected in feces. In daily urine were detected and preliminary identified in addition to unchanged substance 7 products its biotransformation: stereoisomer of DHQ, methylated metabolite of DHQ, stereoisomer of methylated metabolite of DHQ, DHQ-glucuronide, stereoisomer of DHQ-glucuronide, methylated metabolite of DHQ-glucuronide and stereoisomer of methylated metabolite of DHQ-glucuronide.

References: Schulz, H.U. et al. (2005) Arzneim.-Forsh./Drug Res. 55:15–22