Pharmacokinetics, metabolism, and saliva output during transidermal and extended-release oral oxybutynin administration in healthy subjects

Objective: To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments. Subjects and Methods: Between October 15 and November 6,2001,13 healthy subjects (7 men and 6 women) participated in a randomized, 2-way crossover study of transdermal (Oxytrol, 3.9 mg/d) and extended-release oral (Ditropan XL,10 mg) oxybutynin. Multiple blood and saliva samples were collected. Pharmacokinetic parameters and total salivary output were assessed. Statistical analyses included 95% confidence intervals, paired t test, analysis of variance, and linear regression. Results: Steady-state plasma concentrations were achieved after the first transdermal application and after the second extended-release oral dose. Mean +/- SD 24-hour oxybutynin areas under the concentration-time curve were comparable during transdermal and oral extended-release treatments, 10.8+/-2.4 vs 9.2+/-3.3 ng . h(-1) . mL(-1), respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2+/-03) was significantly lower (P<.001) than after extended-release oral administration (4.1+/-0.9). Mean plasma concentrations were less variable during transdermal compared with extended-release oral administration. Mean +/-SD saliva output was greater during transdermal than extended-release oral treatment (15.7+/-93 vs 12.2+/-6.8 g, respectively; P=.02). Lower N-desethyloxybutynin during transdermal application was associated with greater saliva output (r=-0.59, P=.04). No clinically important treatment-related adverse effects were observed. Conclusions: Transdermal oxybutynin administration results in greater systemic availability and minimizes metabolism to N-desethyloxybutynin compared with extended-release oral administration. Lower N-desethyloxybutynin plasma concentration and greater saliva out ut,P during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.