Preclinical Pharmacodynamic and Pharmacokinetic Studies of Investigational New Drngs PDF
By:Patricia Noker,Southern research inst birmingham al
Published on 1998 by
During the contract pharmacokinetic, pharmacodynamic, bioavailability and metabolism studies were conducted on the following compounds under development by the U.S. Army Medical Research Acquisition Activity: the anti-cyanotic agents, WR 242511 and PAHP; the nerve agent antidote, HI-6; the anti-malarial agents, WR 238605, WR 243251 and isomers, WR 250547 and WR 250548, artelinic acid and N-desbutylhalofantrine. Major findings indicated that a metabolite of WR 242511 is responsible for the production of methemoglobinemia; dogs and rats may metabolize PAHP differently; significant clinical interactions do not appear to occur when WR 238605 is given to dogs along with other schizonticidal agents; artelinic acid is extensively metabolized and radioactivity derived from 14Cartelinic acid is widely distributed in rats; the dose of artelinic acid required to elicit a pharmacodynamic effect in rats, as assessed by mortality and clinical signs of toxicity, is almost 20-fold lower when the compound is given intravenously, compared to orally; the pharmacodynamic effects of WR 243251 appear to be predominantly associated with its R-isomer, WR 250547; radioactivity derived from 14Cn-desbutylhalofantrine is widely distributed in rats.
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