Blood dispositions of mitomycin C and a lipophilic prodrug after intramuscular and intravenous administration in liposomes and O/W emulsion.

Abstract

The potential utility of lipidic dosage forms incorporating a lipophilic prodrug of mitomycin C [an antitumor agent] (MMC), nonyloxycarbonyl MMC, was evaluated by determining blood levels after i.m. and i.v. administration of different formulations in rats. After i.m. injection of MMC in the forms of liposomes, O/W [oil/water] emulsion and dimethyl sulfoxide (DMSO) solution, MMC appeared in the circulation at an early stage and disappeared rapidly regardles of dosage form. Neither MMC nor prodrug could be detected in the blood after injection of the prodrug in lipidic dosage forms. Formulations consisting of prodrug and lipidic carriers would apparently show less severe systemic side effects than formulations of MMC for local injection. In the same experiment, the lipid component of liposomes was detected in the blood, but that of emulsion did not appear in the blood. Although i.v. injection of the prodrug in DMSO solution resulted in rapid conversion to MMC, slow conversion was observed when this prodrug was administered in the form of O/W emulsion. The prodrug was apparently retained in these carriers and released gradually, followed by subsequent rapid conversion to MMC in the plasma. Wide potential applicability of these systems for controlling the fate of MMC was demonstrated.