Guay D R, Awni W M, Findlay J W, Halstenson C E, Abraham P A, Opsahl J A, Jones E C, Matzke G R
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415.
Clin Pharmacol Ther. 1988 Jan;43(1):63-71. doi: 10.1038/clpt.1988.12.
The pharmacokinetics and pharmacodynamics of codeine and its metabolites codeine glucuronide, morphine, and morphine glucuronide were assessed after the administration of a single 60 mg oral dose of codeine sulfate and a single 60 mg intravenous dose of codeine phosphate in six healthy volunteers and six patients on chronic hemodialysis. Plasma and urine drug and metabolite concentrations were determined by sensitive and specific RIA procedures. Pharmacodynamics were assessed by pupillometry and vital sign determinations. Codeine elimination half-life and mean residence time were increased significantly in the hemodialysis group (18.69 +/- 9.03 hours and 12.77 +/- 7.09 hours, mean +/- SD, respectively) compared with the healthy volunteer group (4.04 +/- 0.60 hours and 3.90 +/- 0.52 hours, respectively). The total body clearance and volume of distribution of codeine were not significantly different between groups. Peak concentrations, times to peak concentrations, and AUCs for the three metabolites were also not significantly different between the groups, in part as a result of significant interpatient variability in the hemodialysis group. Examination of pupillometry and vital sign data did not reveal clinically significant differences in pharmacodynamics between the groups. Adjustment of dosage regimen may be required in some patients with uremia receiving multiple-dose codeine therapy.
在6名健康志愿者和6名接受慢性血液透析的患者中，分别单次口服60 mg硫酸可待因和单次静脉注射60 mg磷酸可待因后，评估了可待因及其代谢产物可待因葡萄糖醛酸苷、吗啡和吗啡葡萄糖醛酸苷的药代动力学和药效学。通过灵敏且特异的放射免疫分析程序测定血浆和尿液中的药物及代谢产物浓度。通过瞳孔测量法和生命体征测定评估药效学。与健康志愿者组（分别为4.04±0.60小时和3.90±0.52小时）相比，血液透析组的可待因消除半衰期和平均驻留时间显著延长（分别为18.69±9.03小时和12.77±7.09小时，均值±标准差）。两组之间可待因的总体清除率和分布容积无显著差异。三组代谢产物的峰值浓度、达峰时间和药时曲线下面积在两组之间也无显著差异，部分原因是血液透析组患者之间存在显著的个体差异。对瞳孔测量法和生命体征数据的检查未发现两组之间在药效学上存在具有临床意义的差异。一些接受多剂量可待因治疗的尿毒症患者可能需要调整给药方案。
