Szeto H H, Umans J G, McFarland J
Am J Obstet Gynecol. 1982 Jul 15;143(6):700-6. doi: 10.1016/0002-9378(82)90118-1.
The extent of fetal exposure to a drug is a function of placental and fetal clearances of the drug. We have compared the placental and fetal clearances of morphine and methadone under steady-state conditions in the chronic pregnant ewe preparation. Morphine and methadone were infused at constant rates to the mother and fetus, and steady-state maternal and fetal plasma concentrations of the drugs were determined by radioimmunoassay. At steady state after maternal infusion of the drugs, the maternal: fetal free drug concentration ratios were 7.6 +/- 0.6 for morphine and 2.9 +/- 0.6 for methadone. The clearance of morphine from mother to fetus (24.9 +/- 3.0 ml/min) was fifteenfold less than that of methadone (390.3 +/- 92.8 ml/min). Fetal nonplacental clearance of methadone (381 +/- 89.1 ml/min) was higher than that of morphine (125.6 +/- 15.3 ml/min). Fetal clearance accounted for 67.4 +/- 3.9% of total morphine clearance from the fetal compartment, but only 42.8 +/- 4.9% of total methadone clearance. Fetal clearance of methadone increases with age in the early third trimester. The lower extent of fetal exposure to morphine compared to methadone is due primarily to a slower clearance of morphine across the placenta from mother to fetus rather than a more rapid clearance of morphine by the fetus.
胎儿对药物的暴露程度是药物胎盘清除率和胎儿清除率的函数。我们在慢性妊娠母羊模型中比较了吗啡和美沙酮在稳态条件下的胎盘清除率和胎儿清除率。将吗啡和美沙酮以恒定速率输注给母体和胎儿，通过放射免疫分析法测定药物在母体和胎儿血浆中的稳态浓度。在母体输注药物达到稳态后，吗啡的母体：胎儿游离药物浓度比为7.6±0.6，美沙酮为2.9±0.6。吗啡从母体到胎儿的清除率（24.9±3.0 ml/min）比美沙酮（390.3±92.8 ml/min）低15倍。美沙酮的胎儿非胎盘清除率（381±89.1 ml/min）高于吗啡（125.6±15.3 ml/min）。胎儿清除率占胎儿体内吗啡总清除率的67.4±3.9%，但仅占美沙酮总清除率的42.8±4.9%。在妊娠晚期早期，美沙酮的胎儿清除率随年龄增加。与美沙酮相比，胎儿对吗啡的暴露程度较低主要是因为吗啡从母体到胎儿通过胎盘的清除较慢，而不是胎儿对吗啡的清除较快。
