Creinin M D, Krohn M A
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Am J Obstet Gynecol. 1997 Dec;177(6):1444-9. doi: 10.1016/s0002-9378(97)70089-9.
Our goal was to evaluate the pharmacokinetics and safety of methotrexate in doses of 50 mg/m2 and 60 mg/m2 in regimens for early abortion.
A randomized controlled trial was performed in women requesting an abortion at < or = 49 days' gestation. Twenty women were treated with intramuscular methotrexate 50 mg/m2 (group 1) or 60 mg/m2 (group 2). Methotrexate levels were determined serially for the first 24 hours, then every 24 hours for 7 days. On the seventh day misoprostol 800 microg was administered vaginally. The misoprostol dose was repeated 24 hours later if abortion did not occur.
Complete abortion occurred in 9 of 10 (90%, 95% confidence interval 56% to 100%) patients in group 1 and all 10 (100%, 95% confidence interval 69% to 100%; p = 0.99) in group 2. Methotrexate levels peaked within 1 to 2 hours and were nondetectable within 48 hours in all patients in group 1 and 72 hours in group 2. Both the maximum concentration of methotrexate and the area under the curve were significantly greater for group 2. Methotrexate clearance rates were 7.89 +/- 1.98 L/hr and 5.55 +/- 0.83 L/hr (p = 0.003), respectively.
The serum levels of intramuscular methotrexate with 50 mg/m2 and 60 mg/m2 regimens indicate that these are safe treatment doses. Methotrexate 50 mg/m2 intramuscularly has the same clearance rates when administered during pregnancy as in a nonpregnant state, and maximum concentrations do not reach sustained toxic levels.
我们的目标是评估在早期流产方案中，50mg/m²和60mg/m²剂量甲氨蝶呤的药代动力学及安全性。
对妊娠≤49天要求堕胎的女性进行了一项随机对照试验。20名女性接受肌肉注射甲氨蝶呤，50mg/m²（第1组）或60mg/m²（第2组）。在最初24小时内连续测定甲氨蝶呤水平，然后在7天内每24小时测定一次。在第7天经阴道给予800μg米索前列醇。如果未发生流产，则在24小时后重复米索前列醇剂量。
第1组10名患者中有9名（90%，95%置信区间56%至100%）完全流产，第2组10名患者全部（100%，95%置信区间69%至100%；p = 0.99）完全流产。第1组所有患者中甲氨蝶呤水平在1至2小时内达到峰值，48小时内检测不到，第2组为72小时内检测不到。第2组甲氨蝶呤的最大浓度和曲线下面积均显著更高。甲氨蝶呤清除率分别为7.89±1.98L/小时和5.55±0.83L/小时（p = 0.003）。
50mg/m²和60mg/m²方案的肌肉注射甲氨蝶呤血清水平表明这些是安全的治疗剂量。妊娠期间肌肉注射50mg/m²甲氨蝶呤的清除率与非妊娠状态时相同，且最大浓度未达到持续中毒水平。
