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

• Published in: Mayo Clinic proceedings Vol. 78; no. 6; pp. 696 - 702
• Main Authors: Appell, Rodney A., Chancellor, Michael B., Zobrist, R. Howard, Thomas, Heather, Sanders, Steven W.
• Format: Journal Article
• Language: English
• Published: Rochester, MN Elsevier Inc 01.06.2003; Mayo Medical Ventures; Elsevier Limited
• Subjects: Administration, Cutaneous; Administration, Oral; Adult; Analysis of Variance; Biological and medical sciences; Cross-Over Studies; Delayed-Action Preparations; Female; Humans; Linear Models; Male; Mandelic Acids - administration & dosage; Mandelic Acids - blood; Mandelic Acids - pharmacokinetics; Medical sciences; Middle Aged; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - blood; Muscarinic Antagonists - pharmacokinetics; Pharmacology. Drug treatments; Reference Values; Saliva - drug effects; Saliva - metabolism; Salivation - drug effects; Time Factors; Urinary system; Human; Urinary system disease; Toxicity; Oral administration; Urinary tract disease; Percutaneous route; Urinary incontinence; Voiding dysfunction; Chemotherapy; Treatment; Antispasmodic agent; Bladder disease; Application method; Oxybutynin; Pharmacokinetics; Saliva
• ISSN: 0025-6196; 1942-5546
• DOI: 10.4065/78.6.696

To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments. 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. 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±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±9.3 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. 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.