Tornblom-Paulander Sara, Tingåker Berith K, Werner Agneta, Liliecreutz Caroline, Conner Peter, Wessel Hans, Ekman-Ordeberg Gunvor
Division of Obstetrics and Gynecology, Department of Woman and Child Health, Karolinska Institute, Stockholm, Sweden.
Department of Obstetrics and Gynecology, Norrköping, Sweden.
Fertil Steril. 2015 Feb;103(2):422-7. doi: 10.1016/j.fertnstert.2014.10.026. Epub 2014 Nov 20.
To investigate the pharmacokinetics, safety, and analgesic efficacy of a novel topical formulation of lidocaine at insertion of an intrauterine device (IUD).
Randomized controlled trial; phase-I and phase-II studies.
University and public hospitals.
PATIENT(S): Women aged ≥18 years who wanted to receive an IUD. Four women were parous in phase I; all in phase II were nulliparous.
INTERVENTION(S): A single, 8.5-mL dose of lidocaine formulation (SHACT) was administered (to the portio, cervix, and uterus) with a specially designed applicator.
MAIN OUTCOME MEASURE(S): The phase-I study (single-arm) was designed for pharmacokinetic assessment; the phase-II study (randomized) was intended for investigation of efficacy and safety.
RESULT(S): From the phase-I study (15 participants), mean pharmacokinetic values were: maximum plasma concentration: 351 ± 205 ng/mL; time taken to reach maximum concentration: 68 ± 41 minutes; and area under the concentration-time curve from 0 to 180 minutes: 717 ± 421 ng*h/mL. Pain relief was observed with lidocaine vs. placebo in the phase-II study (218 women, randomized). Mean visual analog scale score for maximum pain during the first 10 minutes after IUD insertion was 36% lower with lidocaine than with placebo (28.3 ± 24.6 vs. 44.2 ± 26.0). Pain intensity was also significantly lower in the lidocaine group at 30 minutes. On average, 3 of 4 patients will have less pain with lidocaine than with placebo. Adverse events were similar in the placebo and lidocaine groups. No serious adverse events were reported.
CONCLUSION(S): Lidocaine provides pain relief lasting for 30-60 minutes for women undergoing IUD insertion, without any safety concerns. Further studies of this lidocaine formulation, for IUD insertion and other clinical applications, are planned.
2011-005660-18 and 2011-006220-20 (EudraCT).
研究一种新型利多卡因局部制剂在宫内节育器（IUD）置入时的药代动力学、安全性及镇痛效果。
随机对照试验；I期和II期研究。
大学医院和公立医院。
年龄≥18岁且希望置入IUD的女性。I期有4名经产妇；II期所有患者均为未产妇。
使用专门设计的涂抹器给予一剂8.5毫升的利多卡因制剂（SHACT）（涂抹于宫颈阴道部、宫颈和子宫）。
I期研究（单臂试验）用于药代动力学评估；II期研究（随机试验）用于疗效和安全性研究。
I期研究（15名参与者）的平均药代动力学值为：最大血浆浓度：351±205纳克/毫升；达到最大浓度所需时间：68±41分钟；0至180分钟浓度-时间曲线下面积：717±421纳克·小时/毫升。在II期研究（218名随机分组的女性）中，与安慰剂相比，利多卡因可减轻疼痛。IUD置入后最初10分钟内最大疼痛程度的平均视觉模拟量表评分，利多卡因组比安慰剂组低36%（28.3±24.6对44.2±26.0）。30分钟时利多卡因组的疼痛强度也显著更低。平均而言，4名患者中有3名使用利多卡因时的疼痛程度低于使用安慰剂时。安慰剂组和利多卡因组的不良事件相似。未报告严重不良事件。
利多卡因可为接受IUD置入的女性提供持续30至60分钟的疼痛缓解，且无任何安全问题。计划对这种利多卡因制剂在IUD置入及其他临床应用方面进行进一步研究。
2011 - 005660 - 18和2011 - 006220 - 20（欧洲临床试验数据库）
