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 bioavailability of oxybutynin 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 Cmax of both oxybutynin (P < 0.0001) and N-desethyloxybutynin (P < 0.0001) and the AUC0-1 of N-desethyloxybutynin (P < 0.05) were significantly larger when oxybutynin was ingested 2 hr after breakfast, than during the fasting, but the AUC0-1 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 of oxybutynin and N-desethyloxybutynin is expected to have minor clinical significance only. However, ingestion of the controlled-release tablet 1 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.
Lukkari
E
E
Department of Clinical Pharmacology, University of Helsinki, Finland.
Aranko
K
K
Juhakoski
A
A
Hakonen
T
T
Neuvonen
P J
PJ
D000328:Adult; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004435:Eating; D005260:Female; D006801:Humans; D008297:Male; D008333:Mandelic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012463:Saliva / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018680:Cholinergic Antagonists; D003692:Delayed-Action Preparations; D008333:Mandelic Acids; C032681:desethyloxybutynin; C005419:oxybutynin