Wolfert C, Merbach M, Stammler G, Emrich O, Meid A D, Burhenne J, Blank A, Mikus G
Abteilung für Klinische Pharmakologie und Pharmakoepidemiologie, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland.
St. Marien- und St. Annastiftskrankenhaus, Ludwigshafen, Deutschland.
Schmerz. 2017 Oct;31(5):516-523. doi: 10.1007/s00482-017-0228-8.
The synthetic opioid tilidine is often used in chronic pain treatment. However, the activation via metabolism in patients with concomitant medication and reduced liver or kidney function is not thoroughly investigated. We therefore studied pain treatment efficacy, health-related quality of live and the metabolism of tilidine in patients with chronic pain.
In all, 48 patients, who were on a stable dose of oral prolonged release tilidine for at least 7 days, were included in this observational multicenter study. Liver and kidney function were assessed in routine blood samples, concentrations of tilidine, nortilidine and bisnortilidine were determined using a validated LC/MS/MS method. Comedication was registered and patients experience with regard to quality of life, pain, gastrointestinal symptoms and adverse events was assessed in standardised questionnaires.
On average a daily dose of 180 mg tilidine was taken. Dose normalized plasma concentrations of the active metabolite nortilidine ranged between 1.6 ng/ml and 76.5 ng/ml (mean 29.2 ± 25.1 ng/ml). Ratios between tilidine and nortilidine were on average 0.28 (median = 0.13, standard deviation = 0.67). Patients were on 1 to 14 different concomitant medications. About 66% of the patients had sufficient pain treatment. Almost no opioid-induced constipation was observed. Only few patients had decreased kidney or liver function which did not result in elevated nortilidine concentrations.
Pain treatment using tilidine resulted in variable nortilidine concentrations which are obviously not strongly influenced by comedication or reduced liver or kidney function. Only a few side effects were observed with almost no opioid-induced constipation.
合成阿片类药物替利定常用于慢性疼痛治疗。然而，对于合并用药且肝肾功能减退患者中通过代谢产生的激活作用尚未进行充分研究。因此，我们研究了替利定在慢性疼痛患者中的疼痛治疗效果、健康相关生活质量及代谢情况。
本观察性多中心研究共纳入48例患者，这些患者口服稳定剂量的长效释放替利定至少7天。通过常规血液样本评估肝肾功能，采用经过验证的液相色谱-质谱联用（LC/MS/MS）方法测定替利定、去甲替利定和双去甲替利定的浓度。记录合并用药情况，并通过标准化问卷评估患者在生活质量、疼痛、胃肠道症状及不良事件方面的体验。
患者平均每日服用180mg替利定。活性代谢产物去甲替利定的剂量标准化血浆浓度在1.6ng/ml至76.5ng/ml之间（平均29.2±25.1ng/ml）。替利定与去甲替利定的平均比值为0.28（中位数=0.13，标准差=0.67）。患者服用1至14种不同的合并用药。约66%的患者疼痛得到充分治疗。几乎未观察到阿片类药物引起的便秘。仅有少数患者肝肾功能减退，但未导致去甲替利定浓度升高。
使用替利定进行疼痛治疗导致去甲替利定浓度存在差异，显然不受合并用药或肝肾功能减退的强烈影响。仅观察到少数副作用，几乎没有阿片类药物引起的便秘。
