Pharmacokinetic Study and Bioavailability of a Novel Synthetic Trioxane Antimalarial Compound 97/63 in Rats

Abstract

Single dose pharmacokinetics study of 97/63 (IND191710,2004)-a trioxane antimalarial developed by Central Drug Research Institute, Lucknow, India was studied in rats following intravenous and oral administration. Serum samples were analysed by HPLC-UV assay. Separation was achieved on a RP-18 column attached with a guard using acetonitrile: phosphate buffer (70:30 %v/v) with UV detector at wavelength 244nm. Serum samples were extracted with n-hexane. Two compartment model without lag time and first order elimination rate was considered to be the best fit to explain the generated oral and intravenous data. Method was sensitive with limit of quantification of 10 ng mL-1. Recovery was >74 %. Terminal half-life and area under curve (AUC) after administering single oral (72 mg kg-1) and intravenous (18 mg kg-1) doses were 10.61 h, 10.57 h, and 1268.97 ng h mL-1, 2025.75 ng h mL-1 respectively. After oral dose, 97/63 was rapidly absorbed attaining maximum concentration 229.24 ng mL-1 at 1 h. Bioavailability of 97/63 was ~ 16%. The lower bioavailability of drug may be due to poor solubility and first pass metabolism and can be improved by prodrug formation of 97/63.