Absorption, tissue disposition, and excretion of fasudil hydrochloride, a RHO kinase inhibitor, in rats and dogs.

Abstract

Fasudil hydrochloride as an intracellular calcium ion antagonist that dilates blood vessels has exhibited a very potent pharmacological effect in the treatment of angina pectoris. The purpose of this study was to determine the absorption, distribution, and excretion profiles of fasudil in rats and beagle dogs, respectively, to clarify its pharmacokinetic pattern. A sensitive and reliable LC-MS/MS method has been developed and established and successfully applied to pharmacokinetic study, including absorption, tissue distribution, and excretion. The results revealed that in the range of 2-6 mg/kg, the pharmacokinetic behavior for instance, AUC and Cmax , in rats was observed in a dose dependent manner. However, the plasma concentrations were indicative of a significant gender difference in the pharmacokinetics of fasudil in rats, in terms of absolute bioavailability and excretion. Interestingly, the resulting data obtained from beagle dogs showed that there was no gender difference in the absolute bioavailability of fasudil hydrochloride after single or repeated administrations. In conclusion, this study characterized the pharmacokinetic pattern fasudil both in rats and beagle dogs through absorption, tissue distribution and excretion study. The findings may be valuable and provide a rationale for further study and its safe use in clinical practice.