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. 2023 Dec;30(1):2180113.
doi: 10.1080/10717544.2023.2180113.

First-in-human study to assess the pharmacokinetics, tolerability, and safety of single-dose oxybutynin hydrochloride administered via a microprocessor-controlled intravaginal ring

Willem de Laat  1 , Lisa Pagan  2   3 , R Karl Malcolm  4 , Maarten Wiegerinck  1 , Victor Nickolson  1 , Bertine Huisman  2   3 , Rik Stuurman  2   5 , Michiel van Esdonk  2 , Naomi Klarenbeek  2
Affiliations

First-in-human study to assess the pharmacokinetics, tolerability, and safety of single-dose oxybutynin hydrochloride administered via a microprocessor-controlled intravaginal ring

Willem de Laat et al. Drug Deliv. 2023 Dec.

Abstract

Polymeric drug-releasing vaginal rings are useful for both local and systemic administration of drugs via the intravaginal route. Typically, they provide continuous sustained or controlled release of drug(s) over extended time periods, thereby avoiding overdose and improving adherence. This first-in-human study (EudraCT number: 2020-0050044-30) evaluated the pharmacokinetics, safety, and tolerability of a single dose of oxybutynin administered by a novel microprocessor-controlled vaginal ring (MedRing). Eight healthy female subjects received an electronically controlled single intravaginal dose of 3 mg oxybutynin hydrochloride (100 mg/mL) dissolved in 1:1 water/propylene glycol administered via MedRing. Following dosing, MedRing was kept in situ for up to 6 h. Blood samples were collected 1 h prior to oxybutynin dosing and subsequently at regular intervals post-dose for the assessment of plasma concentrations of oxybutynin and its active metabolite N-desethyloxybutynin. The results showed that MedRing efficiently administered oxybutynin via the intravaginal route, resulting in plasma oxybutynin levels comparable to orally administered oxybutynin. The mean ± standard deviation pharmacokinetic parameters for oxybutynin were Cmax 5.4 ± 2.7 ng/mL, AUCinf 34.9 ± 17.4 h ng/mL, t1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were Cmax 3.9 ± 2.5 ng/mL, AUCinf 51.1 ± 43.1 h ng/mL, t1/2 7.7 ± 5.9 h. No serious adverse events were reported. The study demonstrates that intravaginal administration of oxybutynin hydrochloride using the MedRing device was well tolerated.

Keywords: N-desethyloxybutynin; Vaginal ring; urinary incontinence.

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Conflict of interest statement

Karl Malcolm, Naomi Klarenbeek, Lisa Pagan, Bertine Huisman, Rik Stuurman, and Michiel van Esdonk declare no conflict of interest. Willem de Laat, Victor Nickolson, and Maarten Wiegerinck are employed by LiGalli.

Figures

Figure 1.
Figure 1.
Illustration of the MedRing vaginal ring device.
Figure 2.
Figure 2.
Individual pharmacokinetic profiles of oxybutynin (A) and N-desethyloxybutynin (B) up to 22 h after intravaginal dosing with 3 mg oxybutynin hydrochloride.
Figure 3.
Figure 3.
Mean (±SD) pharmacokinetic profiles of oxybutynin and N-desethyloxybutynin, 2 h and 6 h (A and B) after removal of MedRing and based on hormonal status (premenopause and postmenopause; C and D) after targeted intravaginal dosing with 3 mg oxybutynin hydrochloride.
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Grants and funding

This study was supported by LiGalli. Karl Malcolm received no funding for this study.

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