[Pharmacokinetic studies of epervudine in rats using HPLC]

Pharmacokinetic properties of active substance of Hevizos ointment (Epervudine) were studied in rats after intravenous, oral and dermal applications. The animals received 10 mg/kg of Epervudine intravenously and orally. For checking of dermal absorption 220 mg of ointment (containing 0.8% of Epervudine) was applied. An HPLC method was developed for determination of Epervudine concentrations in serum. The method meets the requirements of precision and accuracy of the kinetic measurements (i.e. CV% is less than 20%) within the concentration range of 50-10,000 ng/ml. The mean serum concentration-time curve after i.v. administration can be characterized by a two-compartment open pharmacokinetic model. The first and second elimination half-lives (t1/2 alpha and t1/2 beta) are 0.14 and 0.31 hours, respectively. These values indicate fast distribution and elimination of compound studied. In the case of oral administration the absorption process conceals the fast distribution, so the mean serum concentration-time curve can be characterized by a one-compartment open pharmacokinetic model. The absorption of Epervudine starts practically prompt. The absorption half-life (t1/2a) is 0.11 hours. Highest serum concentrations were measured from 20 to 90 minutes after treatment. The elimination half-life (t1/2e) is 1.53 hours. The ratio of areas under serum level curves following oral and intravenous administration proves a good bioavailability (90%) of Epervudine. After dermal application Epervudine does not absorb.