Premium
Effect of the Proton Pump Inhibitor Omeprazole on the Pharmacokinetics of Extended‐Release Formulations of Oxybutynin and Tolterodine
Author(s) -
Dmochowski Roger,
Chen Andrew,
Sathyan Gayatri,
MacDiarmid Scott,
Gidwani Shalini,
Gupta Suneel
Publication year - 2005
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005278055
Subject(s) - tolterodine , omeprazole , oxybutynin , pharmacokinetics , chemistry , metabolite , pharmacology , active metabolite , lansoprazole , proton pump inhibitor , bioequivalence , bioavailability , medicine , biochemistry , overactive bladder , alternative medicine , pathology
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 capules 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 AUC ∞ 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.