Disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments in rats.
Disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments in rats.
复制标题
布比卡因及其代谢物在大鼠母体、胎盘和胎儿室中的分布。
DOI：
10.1097/00000542-200010000-00031
复制
发表时间：
2000
期刊：
影响因子：
8.8
通讯作者：
Cooper,TB
中科院分区：
文献类型：
--
作者：
Morishima,HO;Ishizaki,A;Zhang,Y;Whittington,RA;Suckow,RF;Cooper,TB
背景本研究旨在确定布比卡因及其代谢产物在母体，胎盘和胎儿室的处置，使用多个采样时间点在长期准备清醒的妊娠rats. METHODS所有动物接受静脉输注布比卡因在0.33毫克的速率。kg-1.在输注结束时或给药后2或4 h分娩胎仔。采用毛细管气相色谱-质谱联用仪测定母体和胎儿的血液和组织样品中布比卡因及其代谢产物的含量。结果布比卡因的消除半衰期为37.7 min，主要代谢产物为3 '-羟基布比卡因。在给药结束时，所有样品中均存在布比卡因和3 '-羟基布比卡因。胎儿与母体血浆中布比卡因的浓度比为0.29，胎盘中为0.63。羊膜中布比卡因浓度最高：母体中为3倍，胎儿血浆中为11倍。在4小时后给药，布比卡因不再检测到在任何母亲和胎儿的样品，而3 '-羟基布比卡因仍然存在于所有组织中，除了胎儿血浆和heart. CONCLUSIONSSThese数据表明，相当数量的布比卡因是由双方的胎盘，以及羊膜和子宫肌层。除胎仔血浆和心脏样本外，所有组织中均存在3 '-羟基布比卡因，即使在母体化合物不再可检出后也是如此。3 '-羟基布比卡因的这种缓慢消除是否会对胎儿-新生儿造成任何不良影响，需要探讨。
BACKGROUNDThis study was designed to determine the disposition of bupivacaine and its metabolites in the maternal, placental, and fetal compartments, using multiple sampling time points in chronically prepared awake pregnant rats.METHODSAll animals received an intravenous infusion of bupivacaine at a rate of 0.33 mg. kg-1. min-1 over a period of 15 min. The fetuses were delivered either at the end of infusion or at 2 or 4 h after dosing. Maternal and fetal blood and tissue samples were obtained for the assays of bupivacaine and its metabolites using capillary gas chromatography-mass spectrometry.RESULTSThe elimination half-life of bupivacaine was 37.7 min. The major metabolite was 3'-hydroxybupivacaine. Bupivacaine and 3'-hydroxybupivacaine were present in all samples at the end of administration. The fetal to maternal concentration ratio of bupivacaine in plasma was 0.29, and in the placenta was 0.63. The amnion contained the highest bupivacaine concentration: threefold higher in the maternal and 11-fold higher than in the fetal plasma. At 4 h after dosing, bupivacaine was no longer detectable in any maternal and fetal samples, whereas 3'-hydroxybupivacaine was still present in all tissues except the fetal plasma and heart.CONCLUSIONSThese data indicate that a considerable amount of bupivacaine is taken up by both sides of the placenta, as well as the amnion and myometrium. 3'-Hydroxybupivacaine was present in all tissues except the fetal plasma and heart samples, even after the parent compound became no longer detectable. Whether this slow elimination of 3'-hydroxybupivacaine causes any adverse effects on the fetus-newborn needs to be explored.