Effect of complexation with arabinogalactan on pharmacokinetics of "guest" drugs in rats: for example, warfarin.

ABSTRACT

A pharmacokinetic study of the warfarin (WF) arabinogalactan (AG) complex with the 1 10 mass ratio after its intragastric introduction to Wistar rats at a dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg) once a day for three days was conducted. It was found that Cmax, T1/2, and AUC of WF in the complex form were lower than after the introduction of blank WF at the same dose, but its elimination (Cl, MRT) was much faster. Significant accumulation (C(min)) and an abrupt increase in plasma concentration after the third introduction were observed for blank WF, whereas the complex showed a much more moderate increase in concentration at this point. However, despite obvious differences in pharmacokinetic parameters, the efficacies of both agents were virtually identical; the complex differed from blank WF by only 15%. This value is rather insignificant and does not impair its anticoagulant activity. Thus, we can conclude that introduction of the WF AG complex is safe in terms of reduction of the bleeding risk and accumulation.