Rectal absorption of [Bis (acetato) ammine dichloro (cyclohexylamine) platinum(IV)] (BMS-182751), a new anti-tumor agent, in rats

The rectal absorption of a platinum anti-tumor agent, [bis (acetato) ammine dichloro (cyclohexylamine) platinum(IV)] (BMS-182751), was investigated in rats. BMS-182751 was co-ground with various carriers to improve its poor a queous solubility. The highest drug dissolution was observed for the co-gro und mixture of BMS-182751 and low molecular (LM) gelatin (1:9, w/w), follow ed by beta-cyclodextrin and polyvinylpyrrolidone. The influence of a suppos itory base or additive on the rectal absorption of BMS-182751 in the drug s tate of crystalline powder or co-ground mixture was examined in vitro using excised rat rectum, A macrogol base gave much higher BMS-182751 permeation across the rat rectum than that from a Pharmasol base. The addition of sod ium caprylate or caprylic acid to the macrogol base markedly enhanced the d rug permeation, and a 3% addition of sodium caprylate to the base afforded maximum drug permeation. Two rectal formulations, the co-ground mixture wit h LM-gelatin plus 3% sodium caprylate in macrogol and the crystalline drug alone plus 3% sodium caprylate in macrogol, as well as an oral aqueous drug suspension, were administered to rats. The C-max and AUG(0-24 h) values fo r platinum from the former suppository were 5.1- and 4.1-fold greater than those from the oral suspension, respectively. The values from the latter su ppository were almost comparable to those from the suspension. These result s suggest that the suppository may provide a promising therapeutic means fo r cancer treatment using this platinum agent.