左旋十八甲基炔诺酮新型避孕微胶囊的研制及其药物动力学…

本研究用乙交酯丙交酯共聚物为囊材，以左旋十八甲基炔诺酮为主药，用新工艺合成了几种新型ＬＮＧ微胶囊，并对它们进行了扫描电镜观察，体外释放度及动物体内释药动力学实验。结果发现，新型ＬＮＧ微胶囊由于其含有一个不含药物的控释层，改变了原来的释药模式，在爆破释放峰后都出现了一个第二释放峰，且这种第二释放峰出现的时相取决于新型微胶囊的粒径即控释层的厚度，它为筛选和控制药物的周期性释放提供了新的模式，展现了广阔     

左旋十八甲基炔诺酮新型避孕微胶囊的研制及其药物动力学的评价

本研究用乙交酯丙交酯共聚物（ＰＬＧＡ）为囊材，以左旋十八甲基炔诺酮（ＬＮＧ）为主药，用新工艺合成了几种新型ＬＮＧ微胶囊，并对它们进行了扫描电镜观察、体外释放度及动物（兔）体内释药动力学实验。结果发现，新型ＬＮＧ微胶囊由于其含有一个不含药物的控释层，改变了原来的释药模式，在爆破释放峰后都出现了一个第二释放峰，且这种第二释放峰出现的时相取决于新型微胶囊的粒径即控释层的厚度，它为筛选和控制药物的周期性释放提供了新的模式，展现了广阔前景。     

左旋18—甲基炔诺酮事后药的药物动力学及药效学研究

本研究为6例健康妇女,在月经周期排卵前后,口服左旋18-甲基炔诺酮(简称18-甲)0.75mg/天,连续七天的药物动力学和药效学。服药期间,每日在服药前取血,此外在第一和第七天服药后1,2,4,8,12和24小时取前臂静脉血,放射免疫法测定血中18-甲水平。药—时曲线表明所有受试者均为开放二室模型,药时方程为C(t)=Ae~(-αt)+Be~(-βt)-(A+B)e~(-kat)。第一天服药后药物动力学参数:达峰时间T_(max)3.74±1.06h,峰值C_(max)=8.91±2.25ng/ml,消除半寿期t_(1/2)β=11.98±2.99h,K_a=0.476±0.1202h,表观分布容积V_d=102.8±35.81L,体内总廊清率Cl=6.34±2.37L/h,血药浓度—时间曲线下面积Auc=136.91±50.58ng/ml/h;第七天药物动力学参数:T_(max)=3.46±1.12h,C_(max)=6.92±2.39ng/ml,t_(1/2)β=14.45±4.55h,K_a=0.4584±0.1640h,V_d=147.81±76.01L,Cl=6.95±4.21L/h,Auc=134.25±56.29ng/ml/h。比较服药第一天和第七天的药物动力学参数经(?)t-test 计算,两者之间无统计学差异。服药期间,每日血标本用RIA法测定雌二醇E_2,孕酮P,促黄体生长激素LH,促卵泡激素FSH,和促泌乳激素PRL。结果发现血内FSH 水平明显偏低,6例中4例LH 峰偏低或消失;有两例孕酮峰消失;E_2及PRL 的变化较小,其值在正常范围内。     

左旋18-甲基炔诺酮两种产品的药代动力学比较

本文报告两种均含0.75mg左旋18-甲基炔诺酮(LNG)的事后片的药代动力学研究。每例对象服药后0～24小时的血清LNG浓度以放射免疫法进行测定;药—时曲线由微机以迭代法进行拟合,均符合二室开放模型。结果显示口服Postinor和国产片以后,血清LNG峰值,C_(max)分别为11.25±3.39(X±SD,下同)和5.89±1.72ng/ml(P<0.001);达峰时间T_(max)分别为1.9l±0.58 和3.08±1.24h,吸收半寿期T_(1/2a)分别是0.88±0.23和1.38±0.69h,服药后0～24h的药-时曲线下面积AUC_(0～24)分别为92.19±34.34和64.40±21.97ng/ml(P<0.05),两者亦均有明显差异。提示口服Postinor以后,LNG的吸收更迅速,更完全。然而服药后分布半寿期T_(1/2α)、消除半寿T_(1/2β)和总廓清率CL在统计学上无显著差异。故提示两种制剂经口服以后在体内的分布和消除过程较为相似。本文结果表明Postinor中LNG剂量可适当减少,而国产事后片若能改进制剂工艺,提高生物利用度也可适当减少剂量。     

左炔诺孕酮宫内缓释系统治疗子宫内膜单纯性增生过长的研究

目的：探讨左炔诺孕酮宫内缓释系统（曼月乐）治疗子宫内膜单纯性增生过长的疗效及可能作用机制。方法：选取 2011年11月—2012年2月门诊应用曼月乐治疗子宫内膜单纯性增生过长的患者60例,观察放置曼月乐6个月后的子宫内膜活检病理变化及经阴道超声测量子宫内膜厚度、子宫动脉血流[阻力指数（RI）、搏动指数（PI）]及月经模式的改变。结果：2例由于阴道持续性点滴出血提前取出,58例子宫内膜转归正常。放置曼月乐前后子宫内膜厚度、RI分别为（1.52±0.33） cm、（0.62±0.14）cm和0.64±0.07、0.79±0.08,差异均有统计学意义（P＜0.05或P＜0.01）,PI分别为1.98±0.51、1.96±0.04,差异无统计学意义（P＞0.05)。放置曼月乐后经量明显减少,24例表现为月经稀发,32例表现为闭经。结论：曼月乐是治疗子宫内膜单纯性增生过长的简单有效方法,对子宫动脉血流的影响是其可能的作用机制。     

使用国产长效避孕皮下埋植剂妇女五年内血清雌二醇、孕酮、左旋18甲基炔诺酮水平

５例使用国产长效避孕皮埋剂（Ｓｉｎｏ－Ｉｍｐｌａｎｔ，以下简称为Ｓｉｎｏ）长达五年以上的妇女，每年末抽血一个周期（即连续４～５周，每周定时抽血一次）。用ＲＩＡ测定血清中雌二醇（Ｅ２），孕酮（Ｐ）和左旋１８甲基炔诺酮（ＬＮＧ）水平。研究结果显示：长期使用Ｓｉｎｏ未出现相似的卵巢内分泌反应。８４％（２１／２５）抽血周期血清Ｅ２水平出现峰值（Ｅ２＞１５０ｐｇ／ｍｌ），以例数计，埋植后１～４年内每年有８０％（４／５）抽血周期血清中Ｅ２显示峰值，第五年为１００％（５／５）。４０％（１０／２５）抽血周期显示黄体活性（Ｐ＞３ｎｇ／ｍｌ），以例数计，埋植第一年为０％（０／５）；第二年为４０％（２／５）；３～５年每年６０％（３／５）表现黄体活性。５例对象中有２例埋植后五年内未见血清Ｐ＞１ｎｇ／ｍｌ，而且这２例分别在埋植后１～２年及３～４年未见Ｅ２峰（Ｅ２＜１５０ｐｇ／ｍｌ）。５例对象埋植前对照周期均有正常的Ｅ２峰和黄体活性。在用Ｓｉｎｏ的５年内抽血周期血清Ｅ２和Ｐ的均值都低于对照周期。在用Ｓｉｎｏ期间，有黄体活性的周期均伴有Ｅ２峰。然而，并非所有有Ｅ２峰的周期都表现黄体活性。在埋植第一年，除第一个月外，血清ＬＮＧ水平低而相对?     

使用国产长效避孕皮下埋植剂妇女第一年血清中左旋18甲基炔诺酮、雌二醇及孕酮水平

10例妇女在月经周期开始的7天内,皮下埋植国产长效避孕埋植剂。埋植后第一年内每周定时抽血一次,用RIA 测定血清中左旋18甲基炔诺酮(LNG),雌二醇(E_2)和孕酮(P)的浓度。血清中LNG 浓度在埋植后开始两周内下降较快,随后两周较缓慢地下降,在埋植后第一年内LNG 浓度几乎呈平稳状态,但显示有明显的个体差异。血清中E_2峰值频繁出现,但随后未见典型的黄体期P 值升高,在高的E_2峰值突然下降时,常伴随阴道流血出现。干扰月经是此埋植剂的主要副反应。     

缓释型前列腺素E2栓用于足月妊娠引产的临床观察

目的 :研究缓释型前列腺素E2 栓用于足月妊娠引产的有效性及安全性。方法 :随机单盲安慰剂对照研究。选择 2 0例 2 5～ 34岁单胎足月无引产禁忌证产妇 ,随机分为用药组 (10人 )和安慰剂组 (10人 )。记录宫颈Bishop评分、用药至临产时间、2 4小时引产成功率、经阴道分娩率、新生儿Apgar评分和产后出血量等。结果 :用药组 4小时宫颈成熟 ,用药至临产平均 8小时 5 5分钟 ,引产成功 9例 ,经阴道分娩率 7例 ,新生儿Apgar评分 1分钟全部 10分 ,产后出血量平均15 5ml;安慰剂组宫颈无变化 ,引产全部失败。结论 :首次于国内通过小样本临床观察后 ,认为缓释型前列腺素E2 栓用于足月引产效果好 ,副反应小 ,使用方便而安全     

Case Report of the Successful Use of Mirena Levonorgestrel Intrauterine System in a Patient with Didelphys Uterus and Obstructed Hemivagina

Background

The Mirena levonorgestrel intrauterine system (IUS; Bayer HealthCare Pharmaceuticals) is frequently used for menstrual suppression in adolescents with special needs. However, the presence of a uterine anomaly is generally considered a contraindication to IUS insertion, thereby excluding a potentially highly effective option for this patient population.

Pharmacokinetics,Safety, and Tolerability of Multiple Doses of the Novel Oxytocin Receptor Antagonist Cligosiban in Development for Premature Ejaculation: Two Randomized Clinical Trials in Healthy Subjects

Background

Cligosiban (formerly IX-01) is a selective oxytocin receptor antagonist being developed for the treatment of premature ejaculation (PE).

The Effect of Food on the Pharmacokinetics of Sildenafil after Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects

IntroductionFemale sexual interest/arousal disorder (FSIAD) affects many women worldwide, but pharmacological treatment options are scarce. A new medicine being developed for FSIAD is an on-demand, dual-route, dual-release drug combination product containing 0.5 mg testosterone (T) and 50 mg sildenafil (S), referred to here as T+S.AimThe aim of this study was to compare the effect of a fed and a fasted state on the pharmacokinetics of sildenafil following administration of T+S.MethodsEighteen healthy women were administered T+S under fed and fasted conditions during 2 separate overnight visits in this randomized, open-label, balanced, 2-period, 2-treatment, 2-sequence crossover study.Main Outcome MeasuresThe pharmacokinetics of sildenafil and its active metabolite N-desmethyl sildenafil were determined over a 24-hour period. Total testosterone was assessed only at a limited number of time points for quality purposes, as sublingual uptake is not expected to be affected by food intake.ResultsThe observed geometric mean ratios (GMRs) and 90% confidence intervals of sildenafil were not all contained within the prespecified bounds (0.80, 1.25). The GMR (90% CI) for plasma AUC_0–last was 1.2753 (0.9706–1.6755); for AUC_0–14h, it was 1.7521 (1.0819–2.8374); and for C_max, it was 1.5591 (0.8634–2.8153). Only lower limits of the CIs fell within the bounds. For N-desmethyl sildenafil, the GMR (90% CI) for AUC_0–last was 0.8437 (0.6738–1.0564); for AUC_0–10h, it was 1.0847 (0.7648–1.5383); and for C_max, it was 1.0083 (0.6638–1.5318). Only the GMRs were contained within bounds. No differences were observed between plasma testosterone C_max and T_max under fed and fasted conditions, which is in line with expectations for a sublingual administration.Clinical ImplicationsThe T+S combination tablet ruptures too late when taken in a fasted state and should therefore not be taken on an empty stomach.Strengths & LimitationsThis is a well-controlled study that provides important insights into the performance characteristics of the delayed-release coating of the combination tablet. The higher variability of the pharmacokinetic parameters in the fasted state was caused by severely delayed rupture in one-third of the women. A reason for this is proposed but the present data do not explain this phenomenon.ConclusionThe pharmacokinetics of sildenafil from this modified-release tablet are more robust under fed conditions as compared to the artificial fasted condition where no food is consumed 10 hours prior to and 4 hours after dosing. The dosing situation under the tested fasting condition does not represent the expected common use of this product. Patients should, however, be instructed not to take the tablet on an empty stomach.Bloemers J, Gerritsen J, van Rooij K, et al. The Effect of Food on the Pharmacokinetics of Sildenafil After Single Administration of a Sublingual Testosterone and Oral Sildenafil Combination Tablet in Healthy Female Subjects. J Sex Med 2019; 19:1433–1443.     

The Effect of Mindfulness-Based Sexual Counseling on Sexual Distress,Attitude Toward Sexuality,and Body Image Concerns in Pregnant Women: A Randomized Controlled Trial

Introduction

Sexual distress during pregnancy can cause a negative attitude toward sexuality during pregnancy, and this can be seen especially in conjunction with body image concerns. This study was conducted to determine the effects of mindfulness-based sexual counseling (MBSC) on sexual distress, attitudes toward sexuality, and body image concerns in pregnant women.

Methods

A randomized controlled trial was conducted in a sample of women who experienced sexual distress presenting to a Healthy Living Center in eastern Turkey. Women (N = 134) were randomly assigned to receive a 4-week, 8-session counseling program based on mindfulness (experimental group; n = 67) or treatment as usual (control group; n = 67). The primary outcome of the study, sexual distress, was assessed using the Female Sexual Distress Scale-Revised. Secondary outcomes included attitude toward sexuality, assessed using the Attitude Scale toward Sexuality during Pregnancy, and body image concerns, using the Body Image Concerns during Pregnancy Scale. Outcomes were compared postintervention, correcting for baseline using analysis of covariance. The study was registered with ClinicalTrials.gov (NCT04900194).

Results

Mean scores for sexual distress (7.69 vs 17.36; P < .001) and body image concerns (57.76 vs 73.88; P < .001) decreased significantly in the mindfulness group compared with the control group. Similarly, mean scores for attitudes toward sexuality significantly improved in the mindfulness group compared with the control group (133.52 vs 105.78; P < .05).

Discussion

MBSC is a promising strategy to help women experiencing sexual distress during pregnancy to reduce their levels of sexual distress, raise their positive attitudes toward sexuality, and lower their body image concerns. Larger clinical trials of MBSC are recommended to support introduction of MBSC into clinical practice.