Pharmacokinetics, Metabolism, and Saliva Output During Transdermal and Extended-Release Oral Oxybutynin Administration in Healthy Subjects

Appell, Rodney A.; Chancellor, Michael B.; Zobrist, R. Howard; Thomas, Heather; Sanders, Steven W.
June 2003
Mayo Clinic Proceedings;Jun2003, Vol. 78 Issue 6, p696
Academic Journal
• 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[sup -1] · ' mL[sup -1], respectively. However, the ratio of area under the curve (N-desethyloxybutynin/oxybutynin) after transdermal administration (1.2 ± 0.3) 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 Ndesethyloxybutynin 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 output during transdermal treatment correspond to the reported low incidence of dry mouth in patients with overactive bladder.


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