Poulsen L, Riishede L, Brøsen K, Clemensen S, Sindrup S H
Department of Clinical Pharmacology, Odense University, Denmark.
Eur J Clin Pharmacol. 1998 Aug;54(6):451-4. doi: 10.1007/s002280050491.
Within the past decade, human experimental pain studies have supported the 50-year-old hypothesis that codeine is a prodrug, which has to be converted to morphine to exert an analgesic effect. This study aimed at evaluating the impact of sparteine phenotype and serum concentrations of morphine on the efficacy of codeine in post-operative pain.
Eighty-one patients with a pain rating of 3 or more on a 0-10 numerical rating scale 0.5 h after surgery were included in the study. The patients were given an oral dose of 100 mg codeine and rated pain with the numerical rating scale 0.5 h and 1 h after medication. Blood for determination of serum concentration of codeine and its metabolites was collected 1 h after medication, and a 12-h urine sample after administration of 100 mg sparteine was used to determine the sparteine phenotype.
Eight patients were poor metabolizers and 66 were extensive metabolizers of sparteine, while the urine samples for the remaining seven patients were lost. In 22 patients, including the eight poor metabolizers, the serum concentrations of both morphine and morphine-6-glucuronide (M6G) were below the limit of determination of the assay, i.e. 1.5 nmol x l(-1) and 2 nmol x l(-1), respectively. A sum of the concentration of these two substances below 10 nmol x l(-1) was found in an additional eight patients. The sum of differences between pre- and post-operative pain ratings did not differ between the two phenotypes (P = 0.60), whereas the 30 patients with serum concentrations of morphine plus M6G below 10 nmol x l(-1) had a marginally significant lower sum than the 51 patients with higher levels of these substances (median 1.5 vs 2.5, P = 0.058).
A low serum concentration of morphine and M6G seems to be common in patients treated with codeine for post-operative pain, and low concentrations of these active substances may be related to decreased efficacy of codeine.
在过去十年中，人体实验性疼痛研究支持了一个有50年历史的假说，即可待因是一种前体药物，必须转化为吗啡才能发挥镇痛作用。本研究旨在评估司巴丁表型和吗啡血清浓度对可待因术后镇痛效果的影响。
81例术后0.5小时疼痛评分在0至10数字评分量表上为3分或更高的患者纳入研究。患者口服100mg可待因，服药后0.5小时和1小时用数字评分量表对疼痛进行评分。服药后1小时采集血样测定可待因及其代谢物的血清浓度，服用100mg司巴丁后采集12小时尿液样本以确定司巴丁表型。
8例患者为司巴丁慢代谢者，66例为司巴丁快代谢者，其余7例患者的尿液样本丢失。在22例患者中，包括8例慢代谢者，吗啡和吗啡-6-葡萄糖醛酸苷（M6G）的血清浓度均低于检测限，即分别低于1.5nmol·L⁻¹和2nmol·L⁻¹。另外8例患者这两种物质的浓度之和低于10nmol·L⁻¹。两种表型患者术前和术后疼痛评分差值之和无差异（P = 0.60），而吗啡加M6G血清浓度低于10nmol·L⁻¹的30例患者的差值之和略低于这些物质水平较高的51例患者（中位数1.5对2.5，P = 0.058）。
在接受可待因治疗术后疼痛的患者中，吗啡和M6G血清浓度低似乎很常见，这些活性物质浓度低可能与可待因疗效降低有关。
