Barzago M M, Omarini D, Aramayona J J, Bonati M
Perinatal Clinical Pharmacology Unit, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
J Pharmacol Toxicol Methods. 1992 Apr;27(2):113-7. doi: 10.1016/1056-8719(92)90030-5.
The effects of different umbilical flow rates on the placental transfer of compounds were studied in order to optimize an in situ placental perfusion model in the rabbit for establishing the most suitable perfusion flow rate range and assessing alterations in the placental architecture related to the umbilical flow. Placental transfer of a tool compound theophylline (TH) at different umbilical flow rates was compared with that of antipyrine (AP), the commonly used indicator of placental exchange, in maternal arterial drug steady-state conditions after a two-step infusion program. Placentas of six rabbits were perfused for 250 min with Earle's enriched bicarbonate buffer at 0.5, 1, 1.5, 2, 3, and 4 mL/min flow rates. Plasma and placental perfusate effluent biochemical parameters, gas exchange, body temperature, and electrocardiogram were recorded. Umbilical arterial perfusion pressure was controlled throughout the experiments. A detailed pharmacokinetic analysis of unbound maternal plasma, perfusate TH, and AP concentrations was made. Placental clearance of TH and AP rose up to the 3 mL/min flow rate and then remained constant. Placental clearance was linear up to 2.0 mL/min for TH and 1.5 mL/min for AP. The umbilical flow rate limit was 1.76 +/- 0.29 mL/min for TH and 1.72 +/- 0.49 mL/min for AP. The clearance index was 0.71 +/- 0.04. The correlation between umbilical flow and perfusion pressure was linear, with mean values from 4 to 25 mmHg. Placental resistances did not change significantly at all flow rates with mean values between 6 and 9 mmHg/mL/min.(ABSTRACT TRUNCATED AT 250 WORDS)
为优化兔原位胎盘灌注模型，以确定最合适的灌注流速范围并评估与脐血流相关的胎盘结构变化，研究了不同脐血流速率对化合物胎盘转运的影响。在两步输注方案后的母体动脉药物稳态条件下，比较了不同脐血流速率下工具化合物茶碱（TH）与常用胎盘交换指标安替比林（AP）的胎盘转运情况。对六只兔的胎盘以0.5、1、1.5、2、3和4 mL/min的流速用Earle氏富碳酸氢盐缓冲液灌注250分钟。记录血浆和胎盘灌注流出液的生化参数、气体交换、体温和心电图。在整个实验过程中控制脐动脉灌注压力。对未结合的母体血浆、灌注液中TH和AP浓度进行了详细的药代动力学分析。TH和AP的胎盘清除率在流速达到3 mL/min时上升，然后保持恒定。TH的胎盘清除率在流速达到2.0 mL/min之前呈线性，AP在流速达到1.5 mL/min之前呈线性。TH的脐血流速率极限为1.76±0.29 mL/min，AP为1.72±0.49 mL/min。清除指数为0.71±0.04。脐血流与灌注压力之间的相关性呈线性，平均值为4至25 mmHg。在所有流速下胎盘阻力均无显著变化，平均值在6至9 mmHg/mL/min之间。（摘要截短为250字）
