Pharmacokinetics of Lidocaine, Bupivacaine, and Levobupivacaine in Plasma and Brain in Awake Rats
Pharmacokinetics of Lidocaine, Bupivacaine, and Levobupivacaine in Plasma and Brain in Awake Rats
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DOI：
10.1097/aln.0b013e3181d9cc54
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发表时间：
2010-06-01
期刊：
影响因子：
8.8
通讯作者：
Asada, Akira
中科院分区：
文献类型：
--
作者：
Ikeda, Yuko;Oda, Yutaka;Asada, Akira
背景：我们比较了利多卡因、外消旋布比卡因(布比卡因)和左旋布比卡因在清醒、自主呼吸的大鼠体内的药代动力学和脑分布。Kg(-1)。Min(-1))，布比卡因(0.1 mg.Kg(-1)。Min(-1))或左旋布比卡因(0.1 mg.Kg(-1)。Min(-1))，连续给药2 h(n=12)。分别在输液过程中和输注结束后2小时采集血样和脑透析液。用微透析法测定脑细胞外液中麻醉药浓度，采用反透析校准法。结果：布比卡因和左旋布比卡因的血浆总浓度和游离浓度以及血浆和脑细胞外液的药代动力学参数均无差异。脑细胞外液中布比卡因浓度显著高于左旋布比卡因(P<；0.001)。尽管三种麻醉药的脑总浓度与血浆总浓度的比值无差异，但布比卡因脑细胞外液浓度与血浆游离浓度的比值显著高于利多卡因和左布比卡因(分别为0.58+/-0.09、0.47+/-0.18和0.40+/-0.09；P分别为0.03和0.003)。结论：虽然三种麻醉药的脑总浓度与血浆总浓度的比值相似，但脑细胞外液体中布比卡因与血浆游离成分的浓度比值显著高于利多卡因和左布比卡因。
Background: We have compared the pharmacokinetics and brain distribution of lidocaine, racemic bupivacaine (bupivacaine), and levobupivacaine in awake, spontaneously breathing rats.Methods: Lidocaine (0.5 mg . kg(-1). min(-1)), bupivacaine (0.1 mg . kg(-1) . min(-1)), or levobupivacaine (0.1 mg . kg(-1) . min(-1)) was continuously administered to rats for 2 h (n = 12, each anesthetic). Blood samples and cerebral dialysate were collected during infusion and for 2 h after termination of infusion. Concentrations of anesthetics in the cerebral extracellular fluid were measured by microdialysis using the retrodialysis calibration method. Tissue-to-plasma partition coefficients calculated from the total (protein-bound and unbound) and unbound concentrations in plasma and brain as well as pharmacokinetic parameters in plasma and cerebral extracellular fluid were compared among the three anesthetics.Results: There were no differences in plasma total or unbound concentrations between bupivacaine and levobupivacaine. Concentrations of bupivacaine in the cerebral extracellular fluid were significantly higher than levobupivacaine (P < 0.001). Despite no differences in the ratio of total brain concentration to total plasma concentration among the three anesthetics, the ratio of cerebral extracellular fluid concentration to plasma unbound fraction of bupivacaine was significantly higher than lidocaine and levobupivacaine (0.58 +/- 0.09, 0.47 +/- 0.18, and 0.40 +/- 0.09, respectively; P = 0.03 and 0.003, respectively).Conclusions: Although the ratio of total brain concentration to total plasma concentrations of lidocaine, bupivacaine, and levobupivacaine was similar, concentration ratio of bupivacaine in the cerebral extracellular fluid to plasma unbound fraction was significantly higher than lidocaine and levobupivacaine.