Gumbleton M, Nicholls P J, Taylor G
Welsh School of Pharmacy, University of Wales Cardiff, UK.
J Pharm Pharmacol. 1990 Oct;42(10):693-7. doi: 10.1111/j.2042-7158.1990.tb06561.x.
Renal blood flow in rats anaesthetized with the combination alphaxolone/alphadolone (3.90 mL min-1 (g tissue)-1) was significantly (P less than 0.05) greater than in rats anaesthetized with ketamine midazolam (3.24 mL min-1 (g tissue)-1, pentobarbitone (3.19 mL min-1 (g tissue)-1), fentanyl/fluanisone midazolam (2.84 mL min-1 (g tissue)-1) or urethane (1.99 mL min-1 (g tissue)-1). Renal blood flow in the urethane anaesthetized rats was significantly (P less than 0.05) lower than in animals anaesthetized with the other anaesthetic regimens, and is consistent with literature reports of a depressive effect of urethane anaesthesia upon xenobiotic renal clearance in the rat. Hepatosplanchnic blood flow was highest in the alphaxolone/alphadolone anaesthetized animals (71.7 mL min-1 kg-1), with the urethane anaesthetized animals demonstrating a significantly (P less than 0.05) lower (33.4 mL min-1 kg-1) blood flow. The fentanyl fluanisone/midazolam (65.4 mL min-1 kg-1), pentobarbitone (61.1 mL min-1 kg-1), and ketamine/midazolam (51.4 mL min-1 kg-1) regimens resulted in hepatosplanchnic blood flows of intermediate magnitude. The observed marked differential effects of the anaesthetic regimens upon renal and hepatosplanchnic blood flows may dramatically influence drug disposition in the experimental animal, and be of significance to laboratory pharmacokinetic studies in which anaesthesia is used.
用α-羟孕酮/α-孕烷二酮联合麻醉的大鼠肾血流量(3.90 mL·min⁻¹·(g组织)⁻¹)显著(P<0.05)高于用氯胺酮/咪达唑仑麻醉的大鼠(3.24 mL·min⁻¹·(g组织)⁻¹)、戊巴比妥麻醉的大鼠(3.19 mL·min⁻¹·(g组织)⁻¹)、芬太尼/氟胺酮/咪达唑仑麻醉的大鼠(2.84 mL·min⁻¹·(g组织)⁻¹)或氨基甲酸乙酯麻醉的大鼠(1.99 mL·min⁻¹·(g组织)⁻¹)。氨基甲酸乙酯麻醉的大鼠肾血流量显著(P<0.05)低于用其他麻醉方案麻醉的动物,这与文献报道的氨基甲酸乙酯麻醉对大鼠异生物质肾清除率的抑制作用一致。肝内脏血流量在α-羟孕酮/α-孕烷二酮麻醉的动物中最高(71.7 mL·min⁻¹·kg⁻¹),氨基甲酸乙酯麻醉的动物血流量显著(P<0.05)较低(33.4 mL·min⁻¹·kg⁻¹)。芬太尼/氟胺酮/咪达唑仑(65.4 mL·min⁻¹·kg⁻¹)、戊巴比妥(61.1 mL·min⁻¹·kg⁻¹)和氯胺酮/咪达唑仑(51.4 mL·min⁻¹·kg⁻¹)方案导致的肝内脏血流量处于中等水平。观察到的麻醉方案对肾和肝内脏血流量的显著差异效应可能会显著影响实验动物体内药物的处置,并且对使用麻醉的实验室药代动力学研究具有重要意义。