The use of phenothiazines to enhance the rectal absorption of water―soluble compounds

Abstract

Abstract The ability of phenothiazines to enhance the rectal absorption of sodium cefoxitin and gentamicin sulphate from aqueous formulations was examined in rats. In the absence of absorption―promoting adjuvants, sodium cefoxitin and gentamicin sulphate bioavailabilities from the rectal compartment were less than 5% of the corresponding intravenous administration. In aqueous microenemas containing 20 mg ml−1 phenothiazine, sodium cefoxitin bioavailability increased to 16–62%, while gentamicin sulphate bioavailability increased to 74–146%. The absorption―promoting potential of chlorpromazine and perphenazine was concentration―dependent, with significant increases in gentamicin sulphate absorption occurring with 1 mg ml−1 chlorpromazine or 2·5 mg ml−1 perphenazine. Maximal gentamicin sulphate bioavailability and serum concentrations were achieved with 10 mg ml−1 chlorpromazine or 20 mg ml−1 perphenazine. The findings indicate that the phenothiazines, which are well absorbed rectally, also significantly enhance the rectal absorption of watersoluble, poorly absorbed compounds.