Metabolism Studies on WR-158,122 in Bile Duct Cannulated Rats and Monkeys

摘要

Pursuing the identity of the fecal products following the oral (or parenteral) administration of WR-158,122-14C posed technical problems. We were unaware of a method of homogenizing (and digesting) feces that did not require chemical and probably degradative action on the sample. In other words how can one get homogeneous fecal samples without changing the composition of the feces themselves. Standard methods including homogenization with acid or alkali or solvent extraction (MeOH) after desiccation did not appear satisfactory for our needs; therefore, we began the development of a new procedure. Studies on the metabolic fate of WR-158,122 (2, 4-diamino-6-(2 naphthylsulfonyl)-quinazoline-2-14C), an antifolate antimalarial compound, have been carried out in 3 rhesus monkeys, 10-bile-duct cannulated rats, 10 bile-duct ligated rats and 8 controls rats. Data on excretion and residual tissue distribution in rats and blood level data and excretion in monkeys are detailed in this reports.