Pharmacokinetics, metabolism, and saliva output during transdermal and extended-release oral oxybutynin administration in healthy subjects.
OBJECTIVE
To compare the pharmacokinetics and adverse effect dynamics of 2 modified-release oxybutynin treatments.


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 +/- 24 vs 9.2 +/- 33 ng x h(-1) x 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 = -059, 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.
Appell
Rodney A
RA
Department of Urology, Baylor College of Medicine, Houston, Tex 77030, USA. rappell@bcm.tmc.edu
Chancellor
Michael B
MB
Zobrist
R Howard
RH
Thomas
Heather
H
Sanders
Steven W
SW
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005260:Female; D006801:Humans; D016014:Linear Models; 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*; D012016:Reference Values; D012463:Saliva / Q000187:drug effects / Q000378:metabolism*; D012472:Salivation / Q000187:drug effects*; D013997:Time Factors
D003692:Delayed-Action Preparations; D008333:Mandelic Acids; D018727:Muscarinic Antagonists; C032681:desethyloxybutynin; C005419:oxybutynin