Beck D H, Schenk M R, Hagemann K, Doepfmer U R, Kox W J
Department of Anesthesiology and Intensive Care Medicine, Charité University Hospital, Humboldt University, Berlin, Germany.
Anesth Analg. 2000 Feb;90(2):431-6. doi: 10.1097/00000539-200002000-00035.
Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg. kg(-1)) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10-20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.
Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.
对乙酰氨基酚的镇痛血浆浓度尚不清楚。我们在一项随机双盲研究中，调查了小剂量（AS；20mg·kg⁻¹）和大剂量（AL；40mg/kg）直肠用对乙酰氨基酚的药代动力学和镇痛效果，并将其与直肠用双氯芬酸（100mg）和对乙酰氨基酚（20mg/kg）的组合（C）在65例接受子宫切除术的女性中进行比较。在诱导标准化全身麻醉后给予栓剂。在24小时内反复评估疼痛（使用10厘米视觉模拟量表测量）和吗啡消耗量（患者自控镇痛）。使用荧光偏振免疫分析法测量对乙酰氨基酚的血浆浓度。40mg/kg对乙酰氨基酚后的解热血浆浓度（10 - 20mg/L）与改善的镇痛效果或减少的阿片类药物需求量无关；20mg/kg对乙酰氨基酚产生低于治疗水平的血浆浓度（<10mg/L）。AL组和AS组分别在4.2小时和3.6小时后达到最大血浆浓度17.2mg/L和10.4mg/L（方差分析，P<0.01）。临床结果的唯一差异是诱导后4小时，对乙酰氨基酚/双氯芬酸组（C组2.0，AS组3.2，AL组3.4）的视觉模拟量表评分较低（方差分析，P<0.05）。成人对乙酰氨基酚的药代动力学与儿童中观察到的相似。镇痛血浆浓度可能高于解热血浆水平，解热血浆水平仅在给予推荐直肠剂量的两倍后才达到。镇痛血浆浓度尚未确定，但可能高于与解热相关的浓度。
成人和儿童的对乙酰氨基酚药代动力学具有可比性。已知可降低体温的血浆浓度并未产生更好的疼痛缓解效果，且仅在给予常规剂量的两倍后才达到。镇痛血浆浓度尚未确定，但可能高于与解热相关的浓度。
