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.

 抽象的

聚合物药物释放阴道环可用于通过阴道内途径局部和全身给药。通常，它们在较长时间内提供药物的连续持续或受控释放，从而避免用药过量并提高依从性。这项首次人体研究（EudraCT 编号：2020-0050044-30）评估了通过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通过 MedRing 接受电子控制单次阴道内剂量的 3 mg 盐酸奥昔布宁 (100 mg/mL) 溶解在 1:1 水/丙二醇中。给药后，MedRing在原位保留长达 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，以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施用奥昔布宁，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，N-去乙基奥昔布宁的C _max 3.9 ± 2.5 ng/mL mL，AUC _inf 51.1 ± 43.1 h ng/mL， t _1/2 7.7 ± 5.9 h。没有报告严重不良事件。研究表明，使用 MedRing 装置阴道内施用盐酸奥昔布宁具有良好的耐受性。