Physiological Pharmaceutics

172 Physiological PharmaceuticsFigure 7.14 Plasma concentration versus time curves of 250 mg diflunisal after oraladministration as a suspension in water () and after rectal administration inmethylcellulose solution at pH 4.5 () and 7 ()pH to 7.0. Control of pH appears to be important to optimize the solubility of a numberof drugs; for example codeine, when delivered in solution at pH 9, produced betterabsorption than at pH 4.3 139 . When delivered in ‘Witepsol’ H15, codeine phosphate canexhibit a plasma concentration profile almost identical to the oral formulation 140 .Natural or hydrogenated soya lecithin added to diclofenac suppositories prolongedabsorption from about 1 h to 6 h in healthy volunteers, without affecting the extent ofabsorption 141 . Interestingly, this study reported that absorption was not affected bydefaecation.AntiemeticsOrally administered antiemetics suffer from quite obvious drawbacks and hence rectaladministration of alizapride, promethazine and metoclopramide have been investigated.Rectal administration of alizapride as a suppository in an unspecified base resulted in amean bioavailability of 61% relative to an intravenous bolus dose 142 . Both alizapride andpromethazine have considerably slower absorption profiles from rectal administrationcompared to either oral or intramuscular administration. In addition, promethazineproduces significant rectal irritation.In human subjects, an aqueous microenema containing metoclopramide resulted inrapid absorption and complete absolute bioavailability. Another advantage of deliveringmetoclopramide rectally is that when given orally, it undergoes extensive first-passmetabolism.Antibacterial agentsMetronidazole is used extensively in the prophylaxis and treatment of anaerobic infections.For practical and economical reasons, attempts have been made to develop rectalmetronidazole formulations. It is absorbed rapidly but incompletely from aqueoussuspension formulations.