The use of phenothiazines to enhance the rectal absorption of water-soluble compounds.
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 water-soluble, poorly absorbed compounds.
D000818:Animals; D002440:Cefoxitin / Q000378:metabolism; D005839:Gentamicins / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012007:Rectum / Q000378:metabolism; D013268:Stimulation, Chemical
D005839:Gentamicins; D010640:Phenothiazines; D002440:Cefoxitin