Intravaginal Delivery of Oxybutynin: An Alternative Administration Route to Improve its Pharmacokinetic and Pharmacodynamic Effects

Background and objective While oxybutynin is the most efficacious oral antimuscarinic treatment to reduce incontinence episodes in patients with an overactive bladder, oxybutynin is often discontinued due to significant side effects. This is hypothesized to be caused by its metabolite. The purpose of the study was to determine whether intravaginal oxybutynin administration leads to fewer anticholinergic side effects than oral oxybutynin. Additionally, the pharmacokinetics (PK), safety, and tolerability were compared. Methods The study had a single-blind, placebo-controlled, three-way cross-over design in 24 healthy women. Participants randomly received repeatedly 2.5 mg intravaginal oxybutynin via the MedRing, 5 mg oral oxybutynin, and placebo. Anticholinergic side effects were assessed with the NeuroCart test battery. Additionally, quantitative electro-encephalography (qEEG), salivary flow, dry mouth symptoms, pharmacokinetics, safety, and tolerability were assessed. Key findings and limitations Neither intravaginal nor oral oxybutynin demonstrated a significant effect on the adaptive tracking test compared to placebo. However, both oxybutynin administration routes resulted in broad qEEG amplitude decreases. Participants reported less dry mouth symptoms, and the saliva weight was significantly higher after intravaginal oxybutynin (estimated difference, 0.51 g [95% confidence interval, 0.16–0.87], p = 0.006). Intravaginal oxybutynin led to a ∼10-fold lower metabolite/parent ratio and was generally safe and well-tolerated. Limitations include the lack of measured cognitive effect in this population, and the ultimately single-blind study conduct because of subtle differences in the appearance of the ring. Conclusions and clinical implications This study provides a solid basis for intravaginal oxybutynin via the MedRing as an alternative route of administration. Intravaginal oxybutynin could be considered an alternative to reduce side effect–related discontinuation rates.