The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro.

Sinomenine, an alkaloid derived from the Chinese medical plant Sinomenium acutum, was studied with regard to its pharmacokinetics and tissue distribution in rats, and to its protein binding ability in the plasma of rats and rabbits and in the solutions of albumin and alpha-1-acid-glycoprotein. An HPLC analytical method was developed for determining sinomenine. The results demonstrated that oral administration with a single dosage at a rate of 90 mg sinomenine/kg in rats achieved about 80% bioavailability, while most of the other pharmacokinetic parameters were similar to the data from the animals treated intravenously. This indicates that oral administration of sinomenine would be appropriate in clinics. In rats, at 45 min after oral dosage, the drug was found to distribute widely in the internal organs, with tissue concentrations (from highest to lowest) in the order of kidneys, liver, lungs, spleen and heart, brain and testicles. At 90 min after dosing, the tissue concentrations in the organs were markedly decreased. The liver and kidneys manifested as the dominant organs with high tissue concentrations that might be responsible for metabolism and elimination of sinomenine. Examination of the protein binding ability showed that sinomenine with 4 microg/ml concentration in the plasma of rats and rabbits or in the albumin solution achieved a protein binding rate of more than 60%, while in the solution of alpha-1-acid-glycoprotein the rate was only about 33%. This result suggests that sinomenine might have much more potent binding ability with albumin than with alpha-1-acid-glycoprotein, resulting from its acidic property.