Effect of Time Interval between Food and Drug Ingestion on the Absorption of Oxybutynin from a Controlled-Release Tablet

Abstra<.t: The effect of time interval between food and drug ingestion on the bioavailability ofoxybutynin was investigated in a randomized. three-phase 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 tablet either in fasting state, 2 hr after breakfast or 1 hr before. The C max of both oxybutynin (P<0.0001) and N-desethyloxybutynin (P<0.0001) and the AUC 0 t of N-desethyloxybutynin (P<0.05) were significantly larger when oxybutynin was ingested 2 hr after breakfast, than during the fasting, but the AUC 0-t of oxybutynin remained unchanged. Breakfast ingested 1 hr after oxybutynin did not affect the pharmacokinetic parameters of oxybutynin or N-desethyloxybutynin. The saliva secretion rate decreased slightly more (P<0.05), when oxybutynin was administered 2 hr after breakfast than during fasting. The effect of food ingestion on the serum concentrations ofoxybutynin and N-desethyloxybutynin is expected to have minor clinical significance only. However, ingestion of the controlled-release tablet I hr before meal increases the likelihood of obtaining constant drug levels with lower peak concentrations 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.