Buchanan M L, Easterling T R, Carr D B, Shen D D, Risler L J, Nelson W L, Mattison D R, Hebert M F
Department of Pharmacy, University of Washington, 1959 NE Pacific Street, H-375 Health Sciences Center, Box 357630, Seattle, WA 98195-7630, USA.
Drug Metab Dispos. 2009 Apr;37(4):702-5. doi: 10.1124/dmd.108.024984. Epub 2008 Dec 30.
The objective of this study was to determine the pharmacokinetic parameters of clonidine during pregnancy compared with previously published data in nonpregnant subjects. Serial blood and urine samples were collected in 17 women during mid to late pregnancy over one steady-state dosing interval to determine clonidine noncompartmental pharmacokinetic parameters (n = 17) and creatinine clearance. In six of these pregnant subjects, maternal and umbilical cord (venous and arterial) plasma samples were collected at the time of delivery for measurement of clonidine concentrations. Clonidine apparent oral clearance was found to be 440 +/- 168 ml/min during pregnancy compared with 245 +/- 72 ml/min as previously reported in nonpregnant subjects (p < 0.0001) (Cunningham et al., 1994). There was a strong correlation (r = 0.82, p < 0.001) between clonidine renal clearance, adjusted for variation in glomerular filtration rate, and urine pH. Umbilical cord to maternal plasma clonidine concentration ratios were 1.0 +/- 0.1 (arterial) and 1.0 +/- 0.1 (venous). In conclusion, clonidine is cleared more rapidly in pregnant women than in nonpregnant subjects. At the time of delivery, the fetus is exposed to similar plasma clonidine concentrations as the mother.
本研究的目的是确定妊娠期间可乐定的药代动力学参数,并与先前发表的非妊娠受试者的数据进行比较。在妊娠中期至晚期的17名女性中,在一个稳态给药间隔内采集系列血液和尿液样本,以确定可乐定的非房室药代动力学参数(n = 17)和肌酐清除率。在这些妊娠受试者中的6名中,在分娩时采集母体和脐带(静脉和动脉)血浆样本,以测量可乐定浓度。发现妊娠期间可乐定的表观口服清除率为440±168 ml/min,而先前报道的非妊娠受试者为245±72 ml/min(p < 0.0001)(坎宁安等人,1994年)。经肾小球滤过率变化校正后的可乐定肾清除率与尿液pH值之间存在强相关性(r = 0.82,p < 0.001)。脐带与母体血浆可乐定浓度比为1.0±0.1(动脉)和1.0±0.1(静脉)。总之,可乐定在孕妇中的清除速度比非妊娠受试者更快。在分娩时,胎儿暴露于与母亲相似的血浆可乐定浓度。