新型左炔诺孕酮/炔雌醇复方避孕贴剂的家兔药代动力学研究

目的:探讨新型左炔诺孕酮(levonorgestrel,LNG)和炔雌醇(ethynylestradiol,EE)在家兔体内的药物动力学特征,评价多次给药后是否出现药物蓄积情况。方法:家兔在单次和多次给药及停止给药后不同时间点耳缘静脉采血,选择放射免疫分析(radioimmunoassay,RIA)法测定各时间点各组家兔雌/孕激素的血药浓度,使用药物动力学软件计算各药物动力学参数并对其进行统计分析。结果:单次给药后受试贴剂低(10cm2)、中(20 cm2)和高剂量(40 cm2)组血清LNG峰浓度(Cmax)分别为1.04±0.12 ng/ml、2.42±0.60 ng/ml和4.90±1.39 ng/ml,3组间有显著差异(P<0.05)。血药浓度-时间曲线下面积(AUC)分别为49.93±9.79h.ng/ml、115.14±34.25 h.ng/ml和251.22±80.55 h.ng/ml,3组间有显著差异(P<0.01);血清EE峰浓度(Cmax)分别为112.00±45.50 pg/ml、139.23±28.23 pg/ml和290.26±66.62 pg/ml,中、高剂量组间有显著差异(P<0.05),而中、低剂量组间无统计学差异(P>0.05)。EE血药浓度-时间曲线下面积(AUC)分别为4.70±1.34 h.ng/ml、6.59±1.23h.ng/ml和16.59±2.33 h.ng/ml,中、高剂量组之间有显著差异(P<0.01)。Evra参比避孕贴剂组血清LNG浓度的Cmax为3.16±1.00 ng/ml,AUC为155.29±46.14 h.ng/ml,与LNG/EE避孕贴剂中剂量组(拟采用的临床试验剂量)相比,两者无显著差异(P>0.05)。中剂量组血清EE浓度与Evra避孕贴剂的相比显著降低(P<0.05)。多次给药后LNG/EE避孕贴剂10 cm2组和20 cm2组在重复给药10次的过程中未出现LNG和EE血药浓度蓄积现象,Evra贴剂组在重复给药4次的过程中未出现LNG和EE血药浓度蓄积现象。结论:中剂量的LNG/EE避孕贴剂具有良好的避孕效果,同时其副作用可能小于Evra。     

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。     

黄体酮阴道环在家兔的药代动力学研究

目的:提供研制可供哺乳期妇女避孕的黄体酮阴道环的药理学依据。方法:将18只去卵巢后2周的新西兰雌兔随机分为3组:阴道环低剂量组(175mg,A组)、高剂量组(350mg,B组)及肌注组(C组),分别在放置阴道环及肌注黄体酮前后不同时点取静脉血,用磁性分离酶联免疫法测定兔血清中黄体酮的浓度,用PK-Graph程序计算药代动力学参数。结果:黄体酮阴道环和黄体酮注射剂在兔体内的药代动力学符合二室开放模型。主要药代动力学参数分别是A组:Tmax:2.23±1.3h,Cmax:47.64±23.58ng/ml,T1/2:818.08±511.77h,AUC:16115.11±8398.88ng·ml·h-1;B组:Tmax:2.03±1.33h,Cmax:74.04±24.57ng/ml,T1/2:730.31±306.49h,AUC:28751.95±7151.95ml·h-1;C组:Tmax:1.54±0.77h,Cmax:138.88±60.96ng/ml,T1/2:2.55±0.89h。其中A组的AUC(56d)明显低于B组,二者有显著性差异(P<0.05);A组和B组的Cmax均低于C组,差异显著(P<0.05);A组和B组的T1/2均明显高于C组(P<0.01),但A、B组间无差异。结论:与传统的黄体酮注射剂相比,黄体酮阴道环的药代动力学参数呈现明显的长效缓释特征。应可成为安全长效且使用方便的哺乳期避孕药具。     

妇女血清可溶性Fas/FasL与反复自然流产的关系初探

目的:探讨妇女血清可溶性Fas/FasL(sFas/sFasL)在反复自然流产(RSA)发病中的作用。方法:采用ELISA法检测62例RSA妇女(RSA组)、34例正常妊娠妇女(正常妊娠组)和34例正常非孕妇女(对照组)血清sFas/sFasL水平。结果:RSA组sFas含量(1051.44±420.87pg/ml)高于对照组(529.49±241.01pg/ml),差异有显著性(P<0.05);正常妊娠组sFas含量(520.19±253.82pg/ml)与对照组相比差异无显著性(P>0.05)。RSA组、正常妊娠组、对照组sFasL含量分别为1.29±0.82ng/ml、1.20±0.85ng/ml、1.32±1.01ng/ml,3组间比较,差异无显著性(P>0.05)。结论:反复自然流产的发生可能与血清sFas水平升高有关,而与血清sFasL无明显相关。     

人绒毛膜匀浆及人脐静脉内皮细胞对人未成熟卵母细胞体外成熟的影响

目的 :研究人早孕绒毛膜匀浆 (UPHC)和人脐静脉内皮细胞 (ECHUV)对人未成熟卵母细胞体外成熟的影响及其作用机理。方法 :应用UPHC培养系统和ECHUV单层细胞培养系统分别培养人未成熟卵母细胞 ,观察卵母细胞体外成熟情况 ;用ELISA方法检测各培养系统中表皮生长因子 (EGF)、粒细胞巨噬细胞集落刺激因子 (GM CSF)和血管表皮生长因子 (VEGF)的浓度。结果 :人未成熟卵母细胞在UPHC和ECHUV培养系统中的成熟率分别为 4 1.0 %和 4 5 .2 % ,明显高于对照组的 14 .3% (P <0 .0 5 ) ;UPHC培养系统和ECHUV培养系统中 ,EGF的浓度分别为 5 2 .6 5± 7.37pg/ml和 5 8.14± 3.0 3pg/ml ,GM CSF的浓度分别为 11.81± 3.76pg/ml和 9.2 0± 2 .5 9pg/ml ,VEGF的浓度分别为 6 1.4 3± 11.38pg/ml和 2 5 6 .5 4± 9.15pg/ml ,均显著高于对照组 (P <0 .0 5 ) ;ECHUV组的VEGF浓度又显著高于UPHC组 (P <0 .0 1) ;<30岁者卵母细胞体外成熟率为 4 2 .6 % ,显著高于 30～ 4 0岁和 >4 0岁的 2 2 .2 %和 13.3% (P <0 .0 5 )。卵 冠 丘复合物体外成熟率为 37.9% ,显著高于裸卵的 2 4 .3% (P <0 .0 5 )。结论 :UPHC和ECHUV促进人未成熟卵母细胞体外成熟 ,其作用与EGF、GM CSF、VEGF有关 ;年龄和卵丘细胞是卵母细胞体外成熟的影响因素。     

巨噬细胞集落刺激因子对卵泡颗粒黄体细胞性激素分泌的影响及其受体的测定

目的　了解人卵泡颗粒黄体细胞中巨噬细胞集落刺激因子 (M CSF)受体的表达 ,M CSF在体外对人卵泡颗粒黄体细胞产生雌、孕激素的影响。方法　采用免疫细胞化学染色法 ,测定 2 0例行卵母细胞浆内单精子注射治疗患者的卵泡颗粒黄体细胞的M CSF受体 ;采用酶免疫分析法 ,测定卵泡颗粒黄体细胞在M CSF(浓度分别为 0、10、2 5、5 0、10 0、2 5 0ng/ml)单独及与促卵泡激素 (FSH ,浓度75IU/ml)联合作用 72h后的上清液中雌二醇 (E2 )和孕酮 (P)的浓度。结果　约 80 %的颗粒黄体细胞膜上M CSF受体阳性。在无FSH存在时 ,M CSF空白对照颗粒黄体细胞培养上清液中E2 浓度为(2 185± 189)pmol/L ,P浓度为 (315 7± 4 0 1)nmol/L ;M CSF为 10～ 10 0ng/ml时 ,E2 浓度在 (2 789± 36 5 )～ (42 82± 318)pmol/L之间 ,P浓度在 (42 5 6± 5 95 )～ (7789± 82 8)nmol/L之间。在有FSH作用时 ,M CSF空白对照的E2 和P浓度分别为 (5 0 4 5± 4 86 )pmol/L和 (86 6 7± 92 3)nmol/L ;M CSF为 10～ 10 0ng/ml时 ,E2 浓度在 (6 5 6 7± 6 73)～ (8373± 935 )pmol/L之间 ,P浓度在 (10 999± 985 )～ (14 990±115 8)nmol/L之间。M CSF促颗粒黄体细胞E2 和P分泌的作用随浓度增加而增强 (P均 <0 0 5 ) ;M CSF与FSH共同作用下颗粒黄体     

控制性超排卵中血清促黄体生成素浓度过低对体外受精-胚胎移植的影响

目的 :探讨控制性超排卵中血清促黄体生成素 (L H)浓度过低对体外受精 -胚胎移植的影响。方法 :为 2 0 0 0年 6月至 2 0 0 1年 8月在本所接受体外受精 (IVF)或卵母细胞单精子显微注射 (ICSI)助孕的不孕症患者 ,对其中具有正常促性腺激素功能的妇女 16 0例采用促性腺激素释放激素激动剂 (Gn RH- a)长方案并单纯用人基因重组促卵泡生长素 (r- FSH)进行控制性超排卵 (COH) ,以注射绒毛膜促性腺激素 (HCG)日血清 L H浓度分为两组 ,低 L H组为血清 L H≤ 0 .5 m IU/ml,对照组为血清 L H>0 .5 m IU/ml,其中低 L H组 72个周期 ,占 4 5 % ,对照组 88个周期 ,总共 16 0个周期。按本所常规方法过行 IVF/ICSI。我们对这 16 0例临床资料进行回顾性分析。结果 :低 L H组平均 r- FSH用药量和用药时间明显多于对照组 (30 .2 1± 8.12支与 2 7.17± 7.99支 ,10 .93± 1.2 5 d与 10 .0 2± 1.18d,P<0 .0 1) ;r- FSH刺激第 8天的血清 L H浓度和雌二醇 (E2 )浓度 (2 .0 5± 1.4 9m IU/ml与 2 .6 2± 1.5 8m IU/ml,182 7.3± 897.6 pg/ml与 2 0 93.3±92 3.7pg/ml,P<0 .0 5 )、注射 HCG日血清 L H浓度和 E2 浓度 (0 .15± 0 .16 m IU/ml与 1.6 0± 0 .92 m IU/ml,1916 .8±989.5 pg/ml与 3495 .2± 938.2 pg/ml,P<0 .0 0 1)     

子宫内膜异位症患者腹膜单核细胞产生IL-6的变化

白细胞介素6(IL-6)介导或增强细胞对免疫细胞分泌物的反应,并在免疫和内分泌系统的通讯网络中起重要的连接作用。子宫内膜异位症(内异症)的病因尚不明确,据推测,由腹膜单核细胞产生的生长因子和炎症性介质可能参与了内异症的致病。IL-6可能是子宫内膜细胞的生长调控因子。 24例因腹痛或不孕而行诊断性腹腔镜检查的病人及行双侧输卵管结扎的妇女为研究对象,分成4组:正常对照(已生育,行输卵管结扎术6例),轻度内异症(修改的AFS标准Ⅰ～Ⅱ期的6例),重度内异症(修改的AFS标准Ⅲ～Ⅳ期,6例)及盆腔粘连患者(既往盆腔感染引起,腹腔镜下无内异症体征6例)。上述患者通过腹腔镜取得腹水经离心取得单核细胞,经孵化、洗涤、组织培养等处理,在有或无内毒素(LPs)(1或10μg/ml),有或无IL-1α(10ng/ml)存在的条件下,检测其产生IL-6的量。 结果:在各组中,对1或10μg/ml的LPS刺激产生的IL-6量分别如下:对照组:1504±169pg/ml,1593±148pg/ml,轻度内异症:1473±188pg/ml,1245±160pg/ml,重度内异症:498±195pg/ml,369±88pg/ml。粘连病人:1448±125pg/ml,1421±205pg/ml。在对照组和粘连组之间,单核细胞对1μg/     

结晶天花粉蛋白脂质体动物抗早孕研究

本文报道结晶天花粉蛋白脂质体(TL)对小白鼠抗早孕作用。结果表明,TL抗早孕剂量为2μg/只,而单纯天花粉剂量为40μg/只,其抗早孕率各为66.7%与70%。说明小剂量TL即有明显的抗旱孕活性。TL体外释放试验证实,6小时其释放率为4.6%,72小时达68.2%。血清孕酮测定结果显示,TL组为3.6±1.2ng/ml,天花粉组为3.9±1.7ng/ml,空白脂质体为9.4±2.3ng/ml,生理盐水组则为12.7±1.4ng/ml。我们的研究结果揭示,TL剂型用于动物抗早孕是成功的。     

The emergency contraceptive drug, levonorgestrel: a review of post-coital oral and peri-coital vaginal administration for prevention of pregnancy

The objective of our study was the evaluation and elucidation of levonorgestrel (LNG) as emergency contraception (EC) administered through oral and vaginal routes. Data regarding post-coital oral and peri-coital vaginal application of LNG were extracted from the literature through MEDLINE database service for years 2001-2010. It was found that a single dose of 1.5 mg LNG or two doses of 0.75 mg LNG 12 h apart were used for EC. Currently, LNG is also on trial for vaginal application as EC in Carraguard gel for 'dual protection'. The oral or vaginal dose of 1.5 mg LNG resulted in peak plasma concentration, C(max) 19.2 or 3.21 ng/ml, with shorter time, T(max) 1.4 or 6.6 h, and greater AUC, 152.7 or 52.5 ng.h/ml, with shorter half-life, 25 or 32 h, respectively. LNG EC inhibited mid-cycle LH surge and delayed or prevented ovulation when administered before ovulation. Mechanism of action of LNG EC appeared to inhibit or delay ovulation. The risk of pregnancy was 4.12%. A single dose of 1.5 mg LNG could reduce the pregnancy rate to 0.7%. Occurrence of ectopic pregnancy following failure of LNG EC was reported. This EC caused no serious adverse effects but was associated with menstrual disturbance. Although widely acceptable, the cost and short-supply to rural areas pose a barrier to access EC for the poor and rural-dwellers, respectively. It was concluded that unlike post-coital oral administration, peri-coital vaginal application of 1.5 mg LNG needs further study to be an alternative option for women to use it for prevention of pregnancy.     

叶酸偶联纳米紫杉醇脂质体在大鼠体内的药物代谢动力学研究

目的探讨叶酸偶联纳米紫杉醇脂质体在大鼠体内的药物代谢动力学。方法将SD大鼠尾静脉注射叶酸偶联纳米紫杉醇脂质体（实验组）及普通紫杉醇脂质体（对照组）,采用高效液相色谱分析紫外（HPLC—UV）法检测两组大鼠体内血药浓度经时变化,Excel绘制药物经时曲线。药物代谢统计分析软件（DAS）模拟房室模型并计算药代动力学参数。结果①紫杉醇标准品血样在0．07-30μg／ml浓度时呈良好的线性关系,浓度测定的日内、日间精密度的相对标准偏差（RSD）值〈6％,高（10．0μg／ml）、中（2．0μg／ml）、低（0．2μg／ml）浓度下的紫杉醇标准品血样的提取回收率均〉90％;②实验组血药浓度经时曲线符合1／C权重的三室模型,对照组符合1／C2权重的二室模型;③实验组药物快、慢分布相半衰期分别是（0．12±0．10）h和（0．40±0．08）h,消除半衰期是（3．29±1．02）h,血浆清除率（CL）是（1．37±0．04）L／（kg·h）,0～t时血药浓度一时间曲线下面积（AUC）及AUC（0～∞）分别是（12．19±0．40）mg／（L·h）和（14．61±0．40）mg／（L·h）;对照组药物分布相半衰期是（0．09±0．08）h,消除半衰期是（2．57±0．51）h,CL是（1．50±0．10）L／（kg·h）,AUC（0～t）及AUC（0～∞）分别是（9．30±0．48）mg／（L·h）和（13．39±0．92）mg／（L·h）;两组消除半衰期、CL、AUC（0-t）和AUC（0～∞）比较,差异均有统计学意义（P〈0．05）。结论叶酸偶联纳米紫杉醇脂质体与普通紫杉醇脂质体均能较快地分布于体内并达到平衡,但是前者半衰期较长,清除速度略快,生物利用度高。     

A pharmacokinetic study with a low-dose oral contraceptive containing 20 microg ethinylestradiol plus 100 microg levonorgestrel.

This study investigated the pharmacokinetics of a dose-reduced oral contraceptive containing 20 microg ethinylestradiol (EE) + 100 microg levonorgestrel (LNG) in 18 young, healthy females. Serum levels of EE and LNG were determined after single and repeated daily oral administration over three treatment cycles, each consisting of 21 treatment days followed by a 7-day treatment-free period. Additionally, the time courses of sex hormone-binding globulin (SHBG), corticoid-binding globulin (CBG) and total and free testosterone serum levels were analyzed. Both active ingredients were rapidly absorbed and maximum concentrations in serum were reached between, on average, 1 and 2 h after single and multiple administrations, respectively. Concentrations of EE increased during repeated daily administration. An approximate two-fold accumulation was calculated based on the comparison of EE area under the curve (AUC) (0-24 h) values determined after the first and the last tablet administration within a treatment cycle. LNG serum concentrations also increased during repeated daily administration, reaching steady-state levels after about 11 days. Based on the comparison of AUC (0-24 h) values determined after the first and the last tablet administration, LNG accumulated approximately by a factor of 3 within a treatment cycle. Steady-state pharmacokinetics of LNG were similar at the end of the first and the third treatment cycles, indicating no further accumulation of LNG beyond a treatment cycle under long-term use of this combined oral contraceptive. The clearance and volume of distribution of LNG decreased and the terminal half-life increased after repeated daily administration, compared with single administration. These effects have also been reported for other LNG/EE combinations. SHBG serum concentrations increased during repeated daily intake by, on average, 1.5-1.6-fold, and for CBG, an average increase of 1.4-1.8-fold was found. Although free testosterone concentrations declined during repeated daily administration by about 40%, total testosterone remained relatively unchanged at a low level. In conclusion, the pharmacokinetics of EE and LNG determined in the present study were in good agreement with those previously reported for 30 microg EE + 150 microg LNG, taking the 33% dose reduction into account.     

Oral misoprostol is rapidly absorbed in postpartum women at term

Objective: To determine the rate of bioavailability of oral misoprostol in the tablet and a new capsule form in women with term pregnancies in the postpartum period. Methods: Twenty-seven women received 400 μg of misoprostol orally after delivery of the fetal vertex in either the standard tablet form or crushed in methylcellulose capsules prepared in our pharmacy. Serum levels of misoprostol free acid, the principal metabolite, were measured at 5-, 15- and 30-min intervals after administration of the medication. The pharmacokinetics of the tablet and capsule groups were then compared. Results: Twenty patients were included in the analysis. At 5 min, there was a trend towards a statistically significant difference in the concentration of misoprostol acid in the tablet group (89 pg/ml) versus the capsule group (20 pg/ml) (p = 0.007). No significant difference in plasma concentration was noted in the two groups at 15 min (tablet group, 256 pg/ml; capsule group, 245 pg/ml; p = 0.85) or 30 min (tablet group, 381 pg/ml; capsule group, 455 pg/ml; p = 0.45). Conclusion: Oral misoprostol is rapidly absorbed and bioavailable in the postpartum period. Misoprostol may prove useful in postpartum management. The novel packaging of misoprostol in capsule form allows for double-blinded studies with similar pharmacokinetics to the standard tablet.     

褪黑素对新生儿脐带血单个核细胞产生细胞因子的影响

目的 探讨褪黑素(melatonin,MLT)对新生儿脐带血单个核细胞(cord blood mononuclear cells,CBMC)产生细胞因子的影响. 方法 体外培养10例健康足月新生儿CBMC,取10例健康成人外周血单个核细胞(peripheral blood mononuclear cells,PBMC)作正常对照,不同浓度MLT(50 pg/ml～50 ng/ml)作为刺激物与CBMC或PBMC共培养,测定培养上清中IL-β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12、IFN-γ及TNF-α水平. 结果 500 pg/ml MLT可刺激CBMC产生较高水平的IL-2[(12.18±7.31)pg/ml]、IL-6[(2091.08±968.58)pg/ml]、IL-8[(2779.04±1168.49)pg/ml]、IL-12[(15.29±6.88)pg/ml]及IFN-γ[(52.22 17.77)pg/ml],与对照组[分别为(6.99±4.94)pg/ml、(1017.06±452.60)pg/ml、(1293.33±791.34)pg/ml、(6.84±2.26)pg/ml、(22.24±10.38)pg/ml]相比,差异有统计学意义(P<0.05);与对照组[(175.63±62.10)pg/ml]相比,不同浓度MLT(50 ng/ml、5 ng/ml、500 pg/ml、50 pg/ml)均可降低CBMC培养上清中TNF-α水平,分别为(24.87±11.21)pg/ml、(18.14±9.44)pg/ml、(31.38±15.28)pg/ml和(28.18±17.35)pg/ml,差异均有统计学意义(P<0.05).5 ng/ml MLT可诱导PBMC产生IL-2、IL-12及IFN-γ,抑制TNF-α的分泌,与对照组比较,差异有统计学意义(P<0.05).比较各自最佳效应浓度的MLT对CBMC(MLT最佳效应浓度为500 pg/ml)和PBMC(MLT最佳效应浓度为5 ng/ml)释放细胞因子IL-2、IL-12、IFN-γ的诱导作用及对TNF-α的抑制作用,除TNF-α外,差异均有统计学意义(P<0.01). 结论 MLT不但可调节PBMC细胞因子的释放,也可调节CBMC细胞因子的释放,且MLT对CBMC分泌细胞因子IL-12、IFN-γ等的调节作用强于其对PBMC的作用.因此,MLT有可能提高新生儿的免疫功能,为临床应用提供了实验依据.     

Comparison of the pharmacokinetics of crinone 8% administered vaginally versus Prometrium administered orally in postmenopausal women(3)

OBJECTIVE: Compare the pharmacokinetics of vaginal progesterone gel (Crinone 8%, 90 mg) with that of oral progesterone (Prometrium, 100 mg). DESIGN: Open-label, randomized, parallel-group protocol. SETTING: Outpatient clinic. PATIENT(s): Twelve healthy postmenopausal women. INTERVENTION(s): Six subjects each were randomized to receive progesterone, which was administered either as 90 mg of progesterone gel (Crinone 8%) given vaginally or 100 mg progesterone in a capsule (Prometrium) given orally. MAIN OUTCOME MEASUREMENT(s): Serum progesterone levels were measured by both radioimmunoassay (RIA) and liquid chromatography-mass spectrometry (LC-MS). RESULT(s): Progesterone given vaginally resulted in greater bioavailability with less relative variability in absorption than oral progesterone (mean AUC(0-24) = 1.48 +/- 0.16 ng. h/mL per milligram vs. 0.035 +/- 0.0052 ng. h/mL per milligram). Mean C(max) for oral progesterone was much lower than that of vaginal progesterone (i.e., 2.20 +/- 3. 06 ng/mL vs. 10.51 +/- 0.46 ng/mL). Mean T(max) occurred earlier for oral progesterone than for Crinone (1.00 +/- 0.41 hours vs. 7.67 +/- 3.67 hours). Radioimmunoassay is inappropriate for determining serum progesterone levels after oral administration, because it provided erroneously high values that were approximately eightfold higher than those obtained with LC-MS. CONCLUSION(s): Crinone (progesterone gel) given vaginally results in greater bioavailability with less relative variability than oral progesterone, thus providing more reliable delivery of progesterone, compared with oral progesterone. Measuring circulating progesterone with use of direct RIA is not appropriate after oral progesterone administration.     

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?