Study On Pharmacokinetics And Metabolism Of Scutellarin

There were few reports on pharmacokinetics and metabolism of scutellarin, although whose pharmacodynamics and clinic application have been studied from the 1970's in China. Pharmacokinetics and metabolism of scutellarin were studied in this dissertation, including absorption pharmacokinetics, tissue distribution and metabolism in rats, absorption pharmacokinetics in Beagle dogs, and its bioavailability in healthy volunteers. The effect of scutellarin on P450 enzymes in rat liver microsomes was evaluated for the first time. These studies provided scientific data for the new drug development and clinic use.1. Absorption pharmacokinetics in ratsTo investigate the absorption pharmacokinetics of scutellarin in rats, a novel HPLC-UV method was firstly established to determine scutellarin in rat plasma. Chromatographic separation was achieved on a Diamonsil C18 column. The mobile phase consisted of methanol-acetonitrile-50 mmol/l NH₄H₂PO₄ buffer (22:15:63, v/v/v, adjusted to pH 2.5 with 1 mol/l phosphoric acid) at a flow-rate of 1.0 ml/min. The ultraviolet detector operated at 335 nm. Linear calibration curves were obtained over the concentration range of 0.050-12.5 μg/ml for scutellarin in rat plasma. The lower limit of quantitation (LLOQ) was 0.050 μg/ml.Individual plasma-concentration data were analyzed by non-compartmental and compartmental analysis, after iv or ig administration of scutellarin at the dose of 40 mg/kg to rats. Mean plasma concentration-time curves of scutellarin were best fitted to three-compartmental models. The absolute oral bioavailability of scutellarin in rats was 4.98%.