Denson D D, Knapp R M, Turner P, Thompson G A
Ther Drug Monit. 1984;6(4):393-8. doi: 10.1097/00007691-198412000-00002.
This study was undertaken to measure the blood concentrations of bupivacaine associated with a single loading dose followed by continuous epidural infusion for the management of the pain of labor and delivery with special reference to the potential for accumulation and toxicity. Four-milliliter venous blood samples were obtained every 15 min following the loading dose until delivery. If inadequate analgesia was observed just prior to delivery, an additional dose of bupivacaine was administered. Bupivacaine concentrations were measured using a double extraction technique followed by gas chromatographic analysis using a nitrogen-specific detector. Clearance, volume of distribution, and rate of absorption were estimated from the blood concentration time data and were 43.39 +/- 11.46 L/h, 67.56 +/- 17.66 L, and 8.97 +/- 3.69 h-1, respectively. Peak serum bupivacaine concentrations were 0.68 +/- 0.14 microgram/ml and occurred 0.58 +/- 0.25 h following administration of the loading dose. The duration of bupivacaine infusion was 3.42 +/- 0.80 h. Serum bupivacaine concentrations at delivery or just prior to administration of a supplemental delivery dose were significantly lower than the peak concentration in all patients (p less than 0.001). Fetal-to-maternal serum concentration ratios were found to be 0.44 +/- 0.16 for the six patients requiring a supplemental delivery dose and 0.44 +/- 0.13 for the six patients receiving bupivacaine only by infusion. The data reported here illustrate that epidural analgesia for labor and delivery achieved using a single 50-mg loading dose followed by a continuous infusion of 12.5 mg/h of bupivacaine will not result in maternal or fetal accumulation or toxicity.
本研究旨在测定布比卡因的血药浓度，该浓度与单次负荷剂量后持续硬膜外输注相关，用于分娩时疼痛的管理，并特别关注其蓄积和毒性的可能性。负荷剂量给药后，每15分钟采集4毫升静脉血样，直至分娩。如果在分娩前观察到镇痛效果不佳，则给予额外剂量的布比卡因。采用双萃取技术，随后使用氮特异性检测器进行气相色谱分析来测定布比卡因浓度。根据血药浓度-时间数据估算清除率、分布容积和吸收速率，分别为43.39±11.46L/h、67.56±17.66L和8.97±3.69h⁻¹。布比卡因血清峰值浓度为0.68±0.14微克/毫升，在负荷剂量给药后0.58±0.25小时出现。布比卡因输注持续时间为3.42±0.80小时。所有患者分娩时或补充分娩剂量给药前的血清布比卡因浓度均显著低于峰值浓度（p<0.001）。对于六名需要补充分娩剂量的患者，胎儿与母体血清浓度比为0.44±0.16，对于六名仅通过输注接受布比卡因的患者，该比值为0.44±0.13。此处报告的数据表明，使用单次50毫克负荷剂量，随后以12.5毫克/小时的速度持续输注布比卡因进行分娩时的硬膜外镇痛，不会导致母体或胎儿蓄积或毒性。
