Physiological Pharmaceutics

Colon and rectal drug delivery 173Ampicillin is poorly absorbed from the rectum and despite many formulationattempts, currently the problem has not been overcome. In addition the drug can producemucosal irritation and diarrhoea.XanthinesTheophylline absorption from a rectal solution is similar to absorption from oral solutions,and generally occurs rapidly and completely. However, absorption from suppositories maybe variable and incomplete. Interestingly, theophylline was well absorbed when delivered ina rectal osmotic delivery device, despite the fact that the level of water available in therectum is very low 143 .The absorption of enprofylline, a bronchodilating xanthine drug which is poorlymetabolised, shows somewhat slow absorption from rectal administration of an aqueoussolution compared with oral intake. Oral absorption was complete, whereas urinary dataindicated an absolute rectal bioavailability of about 89% 144 .Drugs in inflammatory bowel diseaseMesalazine is the locally active moiety of sulphasalazine used in the treatment ofinflammatory bowel disease. It is liberated from the orally administered parent drug in thecolon by bacterial splitting of an azo bond. It is frequently delivered by enema, particularlyin patients with ulcerative colitis of the distal colon. As the adverse effects of oralsulphasalazine are ascribed to the sulphapyridine moiety, colon specific formulations havebeen developed which have low systemic bioavailability without the sulphapyridine group.Rectal instillation of corticosteroids is a well-established approach for the treatmentof inflammatory bowel disease. Corticosteroids which show high efficacy and low systemicdrug concentrations are preferred, in order to minimise adrenal suppression and otheradverse effects inherent in steroid therapy. Rectal prednisolone, budesonide, tixocortolpivalate and beclomethasone diproprionate appear to interfere less with adrenocorticalfunction than hydrocortisone acetate, prednisolone-21-phosphate and betamethasone. Inclinical practice, steroid enemas prove to be difficult to retain because of their large volume,and hence foams are used.Cardiovascular active drugsRate-controlled rectal drug delivery of nifedipine by an osmotic delivery device in healthyvolunteers resulted in a steady-state plasma concentration, with the low input rate resultingin a lowering of blood pressure without concurrent reflex tachycardia.Rectal irritation and damageLong term rectal application of drugs has been reported to produce irritation, rectalbleeding pain and even ulceration. Ergotamine tartrate suppositories used at a dose rangeof 1.5 to 9 mg over a period of between 1 and 8 years can produce rectal damage, probablydue to mucosal ischaemia produced by the alkaloid 145 .Rectal ulceration and stenoses have also been reported in patients using suppositoriescontaining dextropropoxyphene 146 , paracetamol, aspirin, caffeine, carbromal, bromisovaland codeine phosphate 147 . Rectal damage only appears to occur after long term dailysuppository use and aspirin, ergotamine and paracetamol appear to cause the most commonproblems.Local irritation can be elicited by rectal application of various drug in humans, forexample oxprenolol solution, diazepam preparations, promethazine suppositories andcarbamazepine suspension, hence tolerability represents an important consideration in thedevelopment of rectal formulations. Interestingly, epithelial cell loss and local inflammatory