Investigation of the Bioavailability of WR-158,122

The purpose of the work performed on this contract was to prepare formulations designed to improve the oral bioavailability of the potent antimalarial, 2,4-diamino-6-(2-naphthylsulfonyl)quinazoline (WR-158,122). During the first six months of the program formulations of the drug were prepared with water soluble excipients such as polyethylene glycols, polyvinyl pyrrolidone, sugars and citric acid. In addition, water soluble derivatives of the drug were prepared in an attempt to improve its in vivo rate of dissolution. A protocol was developed for determining the bioavailability of various formulations using WR-158,122-2-14C. In those studies where unlabelled WR-158,122 was orally administered, plasma was analyzed for drug equivalents using a fluorospectrophotometric assay. A corn oil-in-water emulsion of WR-158,122 was administered p.o. to rats and beagle dogs. In addition, substantive progress has been made in the preparation of solid dosage forms using water soluble polymers to encapsulate corn oil and the drug. See also report dated Oct 74, AD/A004 186.