肝硬化患者中甲氧氯普胺的药代动力学
Pharmacokinetics of metoclopramide in patients with liver cirrhosis.
作者信息
Magueur E, Hagege H, Attali P, Singlas E, Etienne J P, Taburet A M
机构信息
Department of Clinical Pharmacy, Bicêtre Hospital, Le Kremlin Bicêtre, France.
出版信息
Br J Clin Pharmacol. 1991 Feb;31(2):185-7. doi: 10.1111/j.1365-2125.1991.tb05511.x.
Abstract
The pharmacokinetics of metoclopramide were investigated after intravenous and oral administration in eight patients with severe alcoholic cirrhosis and in eight healthy volunteers. As a consequence of a 50% lower clearance (0.16 +/- 0.07 vs 0.34 +/- 0.09 l h-1 kg-1, plasma drug concentrations and the half-life of metoclopramide were greater in patients following both routes of drug administration. Volume of distribution (3.1 +/- 0.8 vs 3.4 +/- 1.2 l kg-1) and absolute bioavailability (79 +/- 19 vs 84 +/- 15%) were similar in the two groups. The adverse effects of metoclopramide observed in patients with marked hepatic impairment are likely to result from increased accumulation of the drug as a result of impaired clearance. Consequently a reduction in dose of 50% is recommended in patients with severe liver cirrhosis.
摘要
对8例重症酒精性肝硬化患者和8名健康志愿者静脉注射和口服甲氧氯普胺后的药代动力学进行了研究。由于清除率降低50%（0.16±0.07对0.34±0.09 l h-1 kg-1），两种给药途径的患者血浆药物浓度和甲氧氯普胺的半衰期均更长。两组的分布容积（3.1±0.8对3.4±1.2 l kg-1）和绝对生物利用度（79±19对84±15%）相似。在明显肝功能损害患者中观察到的甲氧氯普胺不良反应可能是由于清除受损导致药物蓄积增加所致。因此，建议重症肝硬化患者将剂量降低50%。
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