Analgesic effect of oral paracetamol 1000 mg/ibuprofen 400 mg, paracetamol 1000 mg/codeine 60 mg, paracetamol 1000 mg/ibuprofen 400 mg/codeine 60 mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study,European Journal of Clinical Pharmacology

当前位置： X-MOL 学术 › Eur. J. Clin. Pharmacol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Analgesic effect of oral paracetamol 1000 mg/ibuprofen 400 mg, paracetamol 1000 mg/codeine 60 mg, paracetamol 1000 mg/ibuprofen 400 mg/codeine 60 mg, or placebo on acute postoperative pain: a single-dose, randomized, and double-blind study
European Journal of Clinical Pharmacology ( IF 2.4 ) Pub Date : 2023-06-22 , DOI: 10.1007/s00228-023-03525-0
Gaute Lyngstad ₁ , Per Skjelbred ₂ , David Michael Swanson ₃ , Lasse Ansgar Skoglund _{1,

2}

Affiliation

Purpose

Combining analgesics with different mechanisms of action may increase the analgesic efficacy. The multidimensional pharmacodynamic profiles of ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 400 mg/paracetamol 1000 mg/codeine 60 mg, and paracetamol 1000 mg/codeine 60 mg and placebo were compared.

Methods

A randomized, double-blind, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 200 patients of both sexes and homogenous ethnicity after third molar surgery (mean age 24 years, range 19–30 years). Primary outcome was sum pain intensity over 6 h (SPI). Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference (SPID), maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat, prevent remedication and harm values, adverse effects, and patient-reported outcome measure (PROM).

Results

Analgesia following ibuprofen and paracetamol combination with or without codeine was comparable. Both were better than paracetamol combined with codeine. Secondary variables supported this finding. Post hoc analysis of SPI and SPID revealed a sex/drug interaction trend in the codeine-containing groups where females experienced less analgesia. PROM showed a significant sex/drug interaction in the paracetamol and codeine group, but not in the other codeine-containing group. Especially females reported known and mild side effects in the codeine-containing groups.

Conclusion

Codeine added to ibuprofen/paracetamol does not seem to add analgesia in a sex-mixed study population. Sex may be a confounding factor when testing weak opioid analgesics such as codeine. PROM seems to be more sensitive than traditional outcome measures.

Trial registration

ClinicalTrials.gov June 2009 NCT00921700.

中文翻译：

口服对乙酰氨基酚 1000 mg/布洛芬 400 mg、对乙酰氨基酚 1000 mg/可待因 60 mg、对乙酰氨基酚 1000 mg/布洛芬 400 mg/可待因 60 mg 或安慰剂对术后急性疼痛的镇痛效果：单剂量、随机、双盲学习

目的

不同作用机制的镇痛药联合使用可能会提高镇痛效果。比较了布洛芬 400 mg/扑热息痛 1000 mg、布洛芬 400 mg/扑热息痛 1000 mg/可待因 60 mg、扑热息痛 1000 mg/可待因 60 mg 和安慰剂的多维药效学特征。

方法

一项随机、双盲、安慰剂对照、平行组、单中心、门诊、单剂量研究，纳入了 200 名同性别、同种族的第三磨牙手术后患者（平均年龄 24 岁，范围 19-30 岁））。主要结果是 6 小时内的总疼痛强度 (SPI)。次要结局是镇痛开始时间、镇痛持续时间、救援药物摄入时间、服用救援药物的患者人数、疼痛强度差总和（SPID）、最大疼痛强度差、达到最大疼痛强度差的时间、需要治疗的人数、预防治疗和危害值、不良反应以及患者报告的结果测量 (PROM)。

结果

布洛芬和扑热息痛联合使用或不使用可待因后的镇痛效果相当。两者均优于扑热息痛联合可待因。次要变量支持了这一发现。对 SPI 和 SPID 的事后分析揭示了含可待因组中性别/药物相互作用的趋势，其中女性经历的镇痛较少。 PROM 在扑热息痛和可待因组中表现出显着的性别/药物相互作用，但在其他含可待因组中则不然。尤其是女性，在含可待因的群体中报告了已知的轻微副作用。