Development and Testing of a Sustained Release System for the Prevention of Malaria.

摘要

Matrices each containing 50 w/w% of 3H-WR-7557 or 14C-WR-158122 in 90L+/10G copolymers of 220,000 and 49,000 respectively have been prepared. The former has been moulded into 1.5 mm diameter beads, the latter cryogenically ground and sieved to 48-180 micron particle size. A third matrix has been prepared containing 50 w/w% acedapsone in the 49,000 molecular weight copolymer used for 14C-WR-158122. The matrices have been used as components of two dual drug systems. System I includes WR-7557 and WR-158122 in a 10/1 wt. ratio. System II includes DADDS and WR-158122 in a 10/1 wt. ratio. Three baboons received System I with a one additional baboon serving as a control to receive a 10/1 mixture of the pure drugs. Two baboons received System II with two additional servings as controls. All baboons received a total drug dose of 50 mg/kg. Excretion data for the tests are discussed. Analysis of tissues excised from System I baboons indicated only slight uptake of carbon-14 and tritium in the three animals receiving the matrix and none by the control. Necropsies of System II baboons have been performed and tissues have been analyzed. As with the System I baboon, very little carbon-14 uptake was observed. However, virtually all tissues contained significant tritium derived from WR-4593.