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 C_max 5.4 ± 2.7 ng/mL, AUC_inf 34.9 ± 17.4 h ng/mL, t_1/2 8.5 ± 3.5 h and for N-desethyloxybutynin were C_max 3.9 ± 2.5 ng/mL, AUC_inf 51.1 ± 43.1 h ng/mL, t_1/2 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.

摘要

聚合药物释放阴道环可用于通过阴道内途径进行局部和全身给药。通常，它们在延长的时间段内提供药物的持续缓释或控释，从而避免过量服用并提高依从性。这项首次人体研究（EudraCT 编号：2020-0050044-30）评估了由新型微处理器控制的阴道环 (MedRing) 施用的单剂量奥昔布宁的药代动力学、安全性和耐受性。八名健康女性受试者接受电子控制的单次阴道内剂量的 3 mg 奥昔布宁盐酸盐 (100 mg/mL) 溶解在 1:1 水/丙二醇中，通过 MedRing 给药。给药后，MedRing 被保存在原位长达 6 小时。在奥昔布宁给药前 1 小时采集血样，随后在给药后定期采集血样，用于评估奥昔布宁及其活性代谢物N-去乙基奥昔布宁的血浆浓度。结果表明，MedRing 通过阴道内途径有效地给予奥昔布宁，导致血浆奥昔布宁水平与口服奥昔布宁相当。奥昔布宁的平均标准差药代动力学参数为Cmax _5.4 ± 2.7 ng/mL，AUC _{inf 34.9} ± 17.4 h ng/mL，t _1/2 8.5 ± 3.5 h，N-去乙基奥昔布宁的 Cmax 为3.9 ± 2.5 ng/mL mL, AUC _inf 51.1 ± 43.1 h ng/mL, t_1/2 7.7 ± 5.9 小时。没有报告严重的不良事件。该研究表明，使用 MedRing 装置阴道内施用奥昔布宁盐酸盐具有良好的耐受性。