EFFECT OF TIME-INTERVAL BETWEEN FOOD AND DRUG INGESTION ON THE ABSORPTION OF OXYBUTYNIN FROM A CONTROLLED-RELEASE TABLET

The effect of time interval between food and drug ingestion on the bio availability of oxybutynin was investigated in a randomized, three-pha se cross-over study in 31 healthy volunteers. The serum concentrations of oxybutynin and the metabolite, N-desethyloxybutynin were measured up to 48 hr after ingestion of a controlled-release 10 mg oxybutynin t ablet either in fasting state, 2 hr after breakfast or 1 hr before. Th e C-max of both oxybutynin (P<0.0001) and N-desethyloxybutynin (P<0.00 01) and the AUC(0-t) of N-desethyloxybutynin (P<0.05) were significant ly larger when oxybutynin was ingested 2 hr after breakfast, than duri ng the fasting, but the AUC(0-t) of oxybutynin remained unchanged. Bre akfast ingested 1 hr after oxybutynin did not affect the pharmacokinet ic parameters of oxybutynin or N-desethyloxybutynin. The saliva secret ion rate decreased slightly more (P<0.05), when oxybutynin was adminis tered 2 hr after breakfast than during fasting. The effect of food ing estion on the serum concentrations of oxybutynin and N-desethyloxybuty nin is expected to have minor clinical significance only However, inge stion of the controlled-release tablet 1 hr before meal increases the likelihood of obtaining constant drug levels with lower peak concentra tions during the dosage interval, and thus ingestion of the controlled -release tablet 0.5-1 hr before food may well improve tolerability and compliance in patients who suffer from adverse reactions.