FETAL DISPOSITION OF DELTA-9-TETRAHYDROCANNABINOL (THC) DURING LATE PREGNANCY IN THE RHESUS-MONKEY
FETAL DISPOSITION OF DELTA-9-TETRAHYDROCANNABINOL (THC) DURING LATE PREGNANCY IN THE RHESUS-MONKEY
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DOI：
10.1016/0041-008x(87)90338-3
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发表时间：
1987-09-15
影响因子：
3.8
通讯作者：
SLIKKER, W
中科院分区：
文献类型：
--
作者：
BAILEY, JR;CUNNY, HC;SLIKKER, W
通过母体桡静脉给三只妊娠晚期（妊娠第146 - 151天）的恒河猴静脉注射0.3毫克/千克的Δ9 - 四氢大麻酚（THC），以量化大麻主要精神活性成分THC的胎盘转运和胎儿分布情况。使用胎盘内插管技术，在给药后0、3、15、30、45、60、90、120和180分钟时，同时从母体子宫静脉和胎盘内动脉采集血液样本。在给药后180分钟采集胎儿血浆、脾脏、睾丸、肺、脑、肝脏、胆汁、肾脏、肾上腺、胸腺和胎盘样本。通过放射免疫分析（RIA）对样本中的THC及其主要代谢物11 - 去甲 - 9 - 羧基 - THC（11 - nor）进行分析。母体（1419纳克/毫升）和胎儿（83纳克/毫升）血浆中THC的峰值分别在给药后3分钟和15分钟出现。到3小时时，母体和胎儿血浆中的THC水平相等（37纳克/毫升）。在给药后24、48、72和96小时（此时THC和11 - nor浓度接近或处于RIA检测灵敏度下限（2纳克/毫升））对母体血浆进行180分钟之后的采样。虽然母体血浆中11 - nor水平在1小时达到峰值（44纳克/毫升），但在胎儿血浆中几乎未检测到11 - nor（<5纳克/毫升）。胎儿脑组织中THC浓度为53 ± 6纳克/克（标准误），肝脏中为114 ± 10纳克/克，而在胎盘、胎儿肝脏和胎儿大脑中未检测到11 - nor。这些数据表明THC能快速穿过胎盘进入胎儿体内。胎儿血浆和组织中缺乏11 - nor表明该代谢物不易穿过胎盘，并且在这个发育阶段胎儿不易将THC代谢为11 - nor。部分数据在1985年美国灵长类动物学家协会会议和1986年畸形学协会会议上发表。这项工作部分由美国国家药物滥用研究所IAG 224 - 830005资助。
Three late-term (Gestational Days 146-151) rhesus monkeys were given 0.3 mg/kg .DELTA.9-tetrahydrocannabinol (THC) intravenously via the maternal radial vein to quantify the placental transfer and fetal dispostion of THC, the major psychoactive component of marijuana. Simultaneous blood samples were obtained from a maternal uterine vein and an intraplacental artery at 0, 3, 15, 30, 45, 60, 90, 120, and 180 min after dosing using an intraplacental cannulation technique. Samples of fetal plasma, spleen, testis, lung, brain, liver, bile, kidney, adrenals, thymus, and placenta were obtained at 180 min postdose. Samples were analyzed for THC and a major metabolite, 11-nor-9-carboxy-THC (11-nor), by radioimmunoassay (RIA). Peak plasma THC values were obtained 3 and 15 min after dosing in the mother (1419 ng/ml) and fetus (83 ng/ml), respectively. By 3 hr, maternal and fetal plasma THC levels were equal (37 ng/ml). Maternal plasma was sampled beyond 180 min at 24, 48, 72, and 96 hr postdose, times at which THC and 11-nor concentrations were either near or at the lower limit of sensitivity for the RIA (2 ng/ml). While maternal plasma 11-nor levels peaked at 1 hr (44 ng/ml), almost no 11-nor was detected in fetal plasma (< 5 ng/ml). Fetal tissue concentrations of THC were 53 .+-. 6 ng/g (SE) for brain and 114 .+-. 10 ng/g for liver, while 11-nor was undetectable in placenta, fetal liver, and fetal brain. These data demonstrate that THC rapidly crosses the placenta and enters the fetus. The lack of 11-nor in fetal plasma and tissues suggests that this metabolite does not readily cross the placenta and that the fetus does not readily metabolize THC to 11-nor at this stage of development. A portion of this data was presented at the 1985 meeting of The American Society of Primatologists and at the 1986 meeting of the Teratology Society. This work was supported in part by NIDA IAG 224-830005.