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Malaria Research and Treatment
Volume 2014, Article ID 759392, 9 pages
http://dx.doi.org/10.1155/2014/759392
Research Article

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

1Pharmacokinetics and Metabolism Division, CSIR-Central Drug Research Institute, Lucknow 226001, India
2Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, India

Received 17 May 2014; Revised 20 July 2014; Accepted 20 July 2014; Published 11 September 2014

Academic Editor: Polrat Wilairatana

Copyright © 2014 Hari Narayan Kushwaha et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 244 nm. 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.