Säwe J, Odar-Cederlöf I
Eur J Clin Pharmacol. 1987;32(4):377-82. doi: 10.1007/BF00543973.
The kinetics of morphine and its glucuronidated metabolites were investigated in seven patients with advanced renal failure. The terminal elimination half life of morphine varied between 1.5 and 4.0 h (mean 2.4 h), the volume of distribution between 2.5 and 6.3 l X kg-1 (mean 4.4 l X kg-1) and the total plasma clearance between 13.3 and 31.3 l X min-1 X kg-1 (mean 21.1 l X kg-1). There were no statistically significant differences between the pharmacokinetic data in the uraemic patients and in a control group of cancer patients with normal kidney function. The concentrations of the glucuronidated metabolites rapidly rose to levels above those of morphine. The elimination half-life of M3G varied between 14.5 and 118.8 h (mean 49.6 h) in the renal failure patients, which is distinctly different from the 2.4 to 6.7 h (mean 4.0 h) found in patients with normal kidney function. There was a significant correlation between the half-life of M3G and renal function estimated as serum urea. Thus, the metabolism of morphine in patients with kidney disease is not significantly impaired. The clinical importance of the high concentrations of glucuronides in uraemic patients is not known.
对7例晚期肾衰竭患者体内吗啡及其葡萄糖醛酸化代谢产物的动力学进行了研究。吗啡的终末消除半衰期在1.5至4.0小时之间（平均2.4小时），分布容积在2.5至6.3升/千克之间（平均4.4升/千克），血浆总清除率在13.3至31.3升/分钟/千克之间（平均21.1升/千克）。尿毒症患者与肾功能正常的癌症患者对照组的药代动力学数据之间无统计学显著差异。葡萄糖醛酸化代谢产物的浓度迅速升至高于吗啡的水平。肾衰竭患者中M3G的消除半衰期在14.5至118.8小时之间（平均49.6小时），这与肾功能正常患者中2.4至6.7小时（平均4.0小时）明显不同。M3G的半衰期与以血清尿素评估的肾功能之间存在显著相关性。因此，肾病患者体内吗啡的代谢未受到明显损害。尿毒症患者体内高浓度葡萄糖醛酸化物的临床意义尚不清楚。
