Payne K A, Roelofse J A, Shipton E A
2 Military Hospital, Wynberg, South Africa.
Anesth Prog. 2002 Winter;49(4):109-12.
Tramadol hydrochloride is an analgesic with mu receptor activity suitable for administration to children as oral drops. As the serum concentration profile and pharmacokinetic parameters in young children are not known via this route, we studied 24 healthy ASA 1 children to determine those parameters. The children's mean age was 5.3 +/- 1.1 years and their mean weight was 17.8 +/- 3.1 kg. They underwent general anesthesia with sevoflurane for dental surgery. The mean duration of anesthesia was 27.9 +/- 10.1 minutes. Tramadol 1.5 mg/kg (this dose was chosen because we have previously shown it to be effective in providing analgesia following pediatric dental surgery) was administered as oral drops 30 minutes before anesthesia. Venous blood samples were taken following the tramadol at 30-minute intervals for 4 hours, every 2 hours for 6 hours, and every 4 hours for 12 hours. The samples were centrifuged and the serum stored at -20 degrees C, and nonstereoselective gas chromatography was used to determine the concentration of (+) and (-) tramadol enantiomers plus their o-demethyltramadol (M1) metabolite concentrations. The tramadol absorption was rapid, the maximum measured serum concentration present occurring before the first sample at 30 minutes. That first sample had a concentration of 352 +/- 83.4 ng/mL. The concentration remained above the 100 ng/mL analgesic level until 6.8 +/- 0.9 hours. The elimination half-life was 3.6 +/- 1.1 hours, the serum clearance 5.6 +/- 2.7 mL/kg/min, and the volume of distribution 4.1 +/- 1.2 L/kg. The (+) enantiomer concentration was 14.2 +/- 4.9% greater than that of the (-) enantiomer. The M1 metabolites had a (-) enantiomer concentration 92.3 +/- 75.1% greater than the (+) enantiomer. From the peak concentration at 4.5 +/- 1.5 hours, the concentration of the metabolite was approximately one third that of the parent drug. The M1 elimination half-life was 5.8 +/- 1.7 hours. Apart from the rapid rise in the serum concentration, these kinetic parameters are similar to those seen in healthy young adults. The concentration profile supports an effective clinical duration in the region of 7 hours.
盐酸曲马多是一种具有μ受体活性的镇痛药，适用于儿童口服滴剂给药。由于通过该途径给药时幼儿的血清浓度曲线和药代动力学参数尚不清楚，我们研究了24名健康的ASA 1级儿童以确定这些参数。这些儿童的平均年龄为5.3±1.1岁，平均体重为17.8±3.1 kg。他们接受了七氟醚全身麻醉以进行牙科手术。平均麻醉持续时间为27.9±10.1分钟。在麻醉前30分钟，以口服滴剂形式给予1.5 mg/kg曲马多（选择该剂量是因为我们之前已证明其在小儿牙科手术后提供镇痛有效）。在给予曲马多后，于30分钟间隔采集静脉血样，持续4小时，之后每2小时采集一次，持续6小时，再之后每4小时采集一次，持续12小时。将血样离心，血清储存在-20℃，并使用非立体选择性气相色谱法测定（+）和（-）曲马多对映体的浓度及其O-去甲基曲马多（M1）代谢物的浓度。曲马多吸收迅速，在30分钟的第一个样本之前就出现了测得的最高血清浓度。第一个样本的浓度为352±83.4 ng/mL。浓度在6.8±0.9小时之前一直保持在100 ng/mL的镇痛水平以上。消除半衰期为3.6±1.1小时，血清清除率为5.6±2.7 mL/kg/min，分布容积为4.1±1.2 L/kg。（+）对映体浓度比（-）对映体高14.2±4.9%。M1代谢物的（-）对映体浓度比对映体（+）高92.3±75.1%。从4.5±1.5小时的峰值浓度开始，代谢物的浓度约为母体药物浓度的三分之一。M1的消除半衰期为5.8±1.7小时。除血清浓度迅速升高外，这些动力学参数与健康年轻成年人的相似。浓度曲线表明临床有效持续时间约为7小时。
