Moss Timothy J M, Doherty Dorota A, Nitsos Ilias, Harding Richard, Newnham John P
Lotteries Commission Perinatal Research Laboratories, School of Women's and Infants' Health, University of Western Australia, Box M094, 35 Stirling Highway, Crawley, WA 6009, Australia. tmoss@
Am J Obstet Gynecol. 2003 Dec;189(6):1751-7. doi: 10.1016/s0002-9378(03)00825-1.
The purpose of this study was to determine the pharmacokinetics of betamethasone in maternal and fetal circulations after maternal or fetal intramuscular administration.
Ewes that bore single fetuses underwent surgery at approximately 96 days of pregnancy for the implantation of fetal and maternal vascular catheters. At approximately 103 days, five ewes were injected intramuscularly with betamethasone (0.5 mg/kg body weight) or five fetuses received ultrasound-guided intramuscular injections of betamethasone (0.5 mg/kg estimated fetal weight). Maternal and fetal blood samples were collected serially for the measurement of plasma betamethasone concentrations.
Fetal injection caused higher peak fetal betamethasone concentrations (341.2+/-23.7 nmol/L) than maternal injection (37.6+/-3.7 nmol/L; P<.001) and greater cumulative betamethasone exposure. The half-life of betamethasone in the fetal circulation was shorter after fetal injection (1.1+/-0.3 hours) than after maternal injection (8.5+/-2.0 hours; P=.006).
The duration of fetal and maternal exposure to betamethasone can be minimized by direct fetal intramuscular administration that, in sheep, affords lung maturation without adverse effects on fetal growth.
本研究旨在确定母体或胎儿肌内注射后倍他米松在母体和胎儿循环中的药代动力学。
怀有单胎的母羊在妊娠约96天时接受手术,植入胎儿和母体血管导管。在约103天时,五只母羊肌内注射倍他米松(0.5mg/kg体重),或五只胎儿接受超声引导下肌内注射倍他米松(0.5mg/kg估计胎儿体重)。连续采集母体和胎儿血样,测定血浆倍他米松浓度。
胎儿注射导致胎儿倍他米松峰值浓度(341.2±23.7nmol/L)高于母体注射(37.6±3.7nmol/L;P<0.001),且倍他米松累积暴露量更大。胎儿注射后倍他米松在胎儿循环中的半衰期(1.1±0.3小时)短于母体注射后(8.5±2.0小时;P=0.006)。
通过直接对胎儿进行肌内注射,可将胎儿和母体接触倍他米松的时间减至最短,在绵羊中,这种方法可促进肺成熟,且对胎儿生长无不良影响。