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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 aqueous solubility. The highest drug dissolution was observed for the co-ground mixture of BMS-182751 and low molecular (LM) gelatin (1:9, w/w), followed by beta-cyclodextrin and polyvinylpyrrolidone. The influence of a suppository base or additive on the rectal absorption of BMS-182751 in the drug state 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 sodium caprylate or caprylic acid to the macrogol base markedly enhanced the drug permeation, and a 3% addition of sodium caprylate to the base afforded maximum drug permeation. Two rectal formulations, the co-ground mixture with 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 Cmax and AUC0-24h values for 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 suppository were almost comparable to those from the suspension. These results suggest that the suppository may provide a promising therapeutic means for cancer treatment using this platinum agent.

Rectal Absorption of (Bis(acetato) ammine dichloro(cyclohexylamine) platinum(IV))(BMS-182751), a New Anti-tumor Agent, in Rats.