羟乙基淀粉输注对大鼠布比卡因药代动力学的影响。

The effect of hydroxyethylstarch infusion on bupivacaine pharmacokinetics in rats.

作者信息

Okutomi T, Matsumoto Y, Saito M, Shimizu M, Hoka S, Kuczkowski K M

机构信息

Department of Anesthesiology, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

Acta Anaesthesiol Belg. 2006;57(3):259-64.

PMID:17067137

Abstract

BACKGROUND

Bupivacaine is the agent most often used for labor analgesia. However, the risk of accidental intravascular injection of this drug and consequent acute systemic toxicity is ever-present. Although hydroxyethylstarch (HES) is preferred over crystalloid for prevention of hypotension during regional anesthesia, the pharmacokinetics of bupivacaine during fluid preloading has not been studied.

METHODS

Twenty-four awake Sprague-Dawley rats were randomly allocated to receive the continuous intravenous infusion of HES 70K, 200K or 400K, or normal saline (NS). After 1 hour of prehydration all animals received bupivacaine, 1mg kg(-1), bolus, followed by a continuous infusion, 0.4mg kg(-1) min(-1) for 15 minutes. After the completion of bupivacaine infusion serial arterial blood samples to determine the plasma bupivacaine concentration were obtained. The plasma concentration-time profile of bupivacaine was fitted to a two-compartment open model, and the estimated intercepts and slopes were used for calculation of standard pharmacokinetic parameters.

RESULTS

The mean peak bupivacaine concentration during HES 400K infusion was significantly lower than during NS infusion (1488 +/- 302 ng ml(-1) vs 2388 +/- 582 ng ml(-1)). Mean volume of distribution in each of the three HES groups was greater than in NS group. Mean area under curves (AUC) during HES 200K and HES 400K infusions were significantly lower than during NS infusion (32534 +/- 4180 and 29619 +/- 4431 min ng ml(-1), respectively, vs 39802 +/- 6268 min ng ml(-1)). Mean total clearance of bupivacaine during HES 200K and HES 400K infusions was significantly higher than during NS infusion (115 +/- 14 and 132 +/- 15 ml min(-1) kg(-1), respectively, vs 92 +/- 14 ml min(-1) kg(-1)).

CONCLUSION

Our results suggest that the increased volume of distribution during HES infusion could be counterbalanced by the increased total clearance, resulting in unchanged half-life or elimination rate constant of bupivacaine.

摘要

背景

布比卡因是最常用于分娩镇痛的药物。然而，该药意外血管内注射及随之而来的急性全身毒性风险始终存在。尽管在区域麻醉期间预防低血压方面，羟乙基淀粉（HES）比晶体液更受青睐，但尚未研究液体预负荷期间布比卡因的药代动力学。

方法

将24只清醒的Sprague-Dawley大鼠随机分配，分别接受70K、200K或400K的羟乙基淀粉或生理盐水（NS）持续静脉输注。预水化1小时后，所有动物均接受1mg kg⁻¹的布比卡因静脉推注，随后以0.4mg kg⁻¹ min⁻¹的速度持续输注15分钟。布比卡因输注结束后，采集系列动脉血样以测定血浆布比卡因浓度。将布比卡因的血浆浓度-时间曲线拟合为二室开放模型，并使用估计的截距和斜率计算标准药代动力学参数。

结果

400K羟乙基淀粉输注期间布比卡因的平均峰值浓度显著低于生理盐水输注期间（1488±302 ng ml⁻¹ 对 2388±582 ng ml⁻¹）。三个羟乙基淀粉组的平均分布容积均大于生理盐水组。200K和400K羟乙基淀粉输注期间的平均曲线下面积（AUC）显著低于生理盐水输注期间（分别为32534±4180和29619±4431 min ng ml⁻¹，对39802±6268 min ng ml⁻¹）。200K和400K羟乙基淀粉输注期间布比卡因的平均总清除率显著高于生理盐水输注期间（分别为115±14和132±15 ml min⁻¹ kg⁻¹，对92±14 ml min⁻¹ kg⁻¹）。