Pharmacokinetics of oxybutynin chloride topical gel: effects of application site, baths, sunscreen and person-to-person transference

Oxybutynin chloride topical gel (OTG; Gelnique®) is an approved formulation for the transdermal administration of oxybutynin, an established antimuscarinic therapy for overactive bladder (OAB). Transdermal administration of oxybutynin minimizes plasma concentrations of the active metabolite N-desethyloxybutynin (N-DEO), which can have anticholinergic adverse effects. In four phase I studies, we separately assessed the effects of OTG application site selection on oxybutynin bioavailability (site-to-site study); the effects of post-application showering on oxybutynin steady-state pharmacokinetics (showering study); the effects of sunscreen application on oxybutynin absorption (sunscreen study); and the person-to-person transfer of oxybutynin through skin-to-skin contact at the application site (transference study). All four studies were open-label, randomized, phase I studies. The site-to-site and showering studies involved repeated administration of OTG to establish steady-state plasma concentrations of oxybutynin and N-DEO; the other two studies involved single doses. Clinical visits were required for pharmacokinetic sampling, supervision of OTG self-application on pharmacokinetic sampling days, showering, sunscreen application and transference experiments. The study included healthy subjects aged 18-45 years. Subjects with conditions requiring medical therapy or interfering with the application of OTG or the interpretation of pharmacokinetic results were excluded. Participants applied OTG (1 g containing oxybutynin chloride 10%, 1.14 mL/dose) once daily to the abdomen, upper arm/shoulder or thigh. Showering occurred 1-6 hours after dosing. Sunscreen was applied 30 minutes before or after OTG application. Abdomen-to-abdomen contact with movement for 15 minutes between treated and untreated participants was conducted 1 hour after dosing. Time points of serial blood sampling for pharmacokinetic analyses varied among studies. Plasma concentrations of oxybutynin and N-DEO (except transference study) were measured. Bioequivalence was tested with ANOVA models for log(e)-transformed plasma exposure (area under the plasma concentration-time curve [AUC]) and maximum plasma concentration (C(max)) to generate 90% confidence intervals (CIs). Oxybutynin and N-DEO exposures (AUCs) from time zero to 24 hours (AUC(24)) were similar for the three application sites, with N-DEO/oxybutynin mean AUC(24) ratios of approximately 0.9. The 90% CIs for thigh-to-abdomen ratios of ox