Effect of the proton pump inhibitor omeprazole on the pharmacokinetics of extended-release formulations of oxybutynin and tolterodine.
This study assessed the effect of the proton pump inhibitor omeprazole on the bioavailability of the extended-release formulations of oxybutynin and tolterodine. Forty-four healthy volunteers received each of 4 treatments in a 4-period crossover design. The treatments consisted of osmotically controlled extended-release oxybutynin chloride tablets at 10 mg/d or extended-release tolterodine tartrate capsules at 4 mg/d, with and without preceding treatment with 20 mg omeprazole daily for 4 days. Blood samples collected predose and at scheduled time points for 36 hours postdose were analyzed for oxybutynin and its active metabolite, N-desethyloxybutynin, or tolterodine and its active 5-hydroxymethyl metabolite, as appropriate. The AUCinfinity ratios for oxybutynin and its metabolite with and without prior omeprazole fell within the 80% to 125% range (accepted as the criterion for bioequivalence), as did those for tolterodine and its active moiety. The peak concentration ratios for oxybutynin and metabolite also conformed to this range; those for tolterodine did not. Increasing gastric pH with omeprazole does not substantially alter the pharmacokinetic properties of extended-release oxybutynin but may alter those of extended-release tolterodine.
Dmochowski
Roger
R
Department of Urology, Vanderbilt University School of Medicine, Medical Center North, Room A1302, Nashville, TN 37232-2765, USA.
Chen
Andrew
A
Sathyan
Gayatri
G
MacDiarmid
Scott
S
Gidwani
Shalini
S
Gupta
Suneel
S
D000293:Adolescent; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003408:Cresols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008333:Mandelic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D010665:Phenylpropanolamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000068737:Tolterodine Tartrate
C109909:5-hydroxymethyl tolterodine; D000897:Anti-Ulcer Agents; D001559:Benzhydryl Compounds; D003408:Cresols; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate; C005419:oxybutynin; D009853:Omeprazole