Aitkenhead A R, Vater M, Achola K, Cooper C M, Smith G
Br J Anaesth. 1984 Aug;56(8):813-9. doi: 10.1093/bja/56.8.813.
Morphine 0.125 mg kg-1 was administered i.v. to 11 normal subjects and nine patients with chronic renal failure requiring regular haemodialysis. Plasma morphine concentrations were measured using high pressure liquid chromatography (HPLC). Although there was considerable individual variation in both groups, mean plasma concentrations of morphine were significantly higher in the patients with renal failure for 15 min after administration. The decay of plasma concentration fitted a three-compartment mamillary pharmacokinetic model in all subjects. Derived values (mean +/- SEM) of T 1/2 alpha, volume of distribution of the second compartment (V2), total volume of distribution at steady state (Vss) and transfer rate constant from the first to the second compartment (k12), were significantly different between groups. Mean values of terminal elimination half-life (T 1/2 gamma) and total body clearance were similar in the two groups. It was concluded that elimination of unchanged morphine is not impaired significantly in patients with chronic renal failure, although accumulation of morphine-3-glucuronide probably occurs. Although the pharmacological effect of morphine is not related temporally to plasma morphine concentrations, the higher values in patients with renal failure may be implicated in their increased sensitivity to the drug.
给11名正常受试者和9名需要定期血液透析的慢性肾衰竭患者静脉注射0.125毫克/千克的吗啡。使用高压液相色谱法（HPLC）测量血浆吗啡浓度。尽管两组个体差异较大，但给药后15分钟内，肾衰竭患者的吗啡平均血浆浓度显著更高。所有受试者的血浆浓度衰减均符合三室乳头状药代动力学模型。两组之间的T 1/2α、第二室分布容积（V2）、稳态时总分布容积（Vss）以及从第一室到第二室的转运速率常数（k12）的推导值（平均值±标准误）存在显著差异。两组的终末消除半衰期（T 1/2γ）和全身清除率平均值相似。得出的结论是，慢性肾衰竭患者中未变化的吗啡消除未受到显著损害，尽管可能会发生吗啡-3-葡萄糖醛酸苷的蓄积。尽管吗啡的药理作用与血浆吗啡浓度在时间上无关，但肾衰竭患者中较高的浓度值可能与他们对该药物的敏感性增加有关。
