酮咯酸氨丁三醇：2至6个月龄术后婴儿的立体特异性药代动力学及单剂量使用
Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months.
作者信息
Lynn Anne M, Bradford Heidi, Kantor Eric D, Andrew Marilee, Vicini Paolo, Anderson Gail D
机构信息
Department of Anesthesia & Pain Management, Seattle Children's Hospital, Seattle, WA 98105, USA.
出版信息
Paediatr Anaesth. 2011 Mar;21(3):325-34. doi: 10.1111/j.1460-9592.2010.03484.x. Epub 2010 Dec 29.
OBJECTIVE
We determined the postoperative pharmacokinetics (PK), safety, and analgesic effects of ketorolac in 14 infants (aged <6 months) receiving a single intravenous (IV) administration of racemic ketorolac or placebo.
BACKGROUND
Information on the PK of ketorolac in infants is limited. Unblinded studies suggest ketorolac may be useful in infants.
METHODS
This double-blinded, placebo-controlled study enrolled 14 infants (aged <6 months) postoperatively. At 6-18 h after surgery, infants were randomized to receive placebo, 0.5 mg·kg(-1), or 1 mg·kg(-1) ketorolac IV. All infants received morphine sulfate as needed for pain control. Blood was collected up to 12-h postdosing. Analysis used noncompartmental and compartmental population modeling methods.
RESULTS
In addition to noncompartmental and empirical Bayes PK modeling, data were integrated with a previously studied data set comprising 25 infants and toddlers (aged 6-18 months). A two-compartmental model described the comprehensive data set. The population estimates of the R (+) isomer were (%CV): central volume of distribution 1130 (10%) ml, peripheral volume of distribution 626 (25%) ml, and clearance from the central compartment 7.40 (8%) ml·min(-1). Those of the S (-) isomer were 1930 (15%) ml, 319 (58%) ml, and 39.5 (13%) ml·min(-1). Typical elimination half-lives were 191 and 33 min, respectively. There was a trend for increased clearance and central volume with increasing age and weight. The base model suggested that clearance of the S (-) isomer was weakly related to age; however, when body size adjustment was added to the model, no covariates were significant. Safety assessment showed no changes in renal or hepatic function tests, surgical drain output, or continuous oximetry between groups. Cumulative morphine administration showed large inter-patient variability and was not different between groups.
CONCLUSION
Stereo-isomer-specific clearance of ketorolac in infants (aged 2-6 months) shows rapid elimination of the analgesic S (-) isomer as reported in infants aged 6-18 months. No adverse effects were seen after a single IV ketorolac dose.
目的
我们测定了14名接受消旋酮咯酸或安慰剂单次静脉注射的6个月以下婴儿术后的药代动力学（PK）、安全性及镇痛效果。
背景
关于酮咯酸在婴儿体内的药代动力学信息有限。非盲法研究表明酮咯酸可能对婴儿有用。
方法
这项双盲、安慰剂对照研究纳入了14名术后婴儿（年龄<6个月）。术后6 - 18小时，婴儿被随机分为接受安慰剂、0.5 mg·kg⁻¹或1 mg·kg⁻¹酮咯酸静脉注射。所有婴儿根据疼痛控制需要接受硫酸吗啡。给药后12小时内采集血液。分析采用非房室和房室群体建模方法。
结果
除了非房室和经验贝叶斯PK建模外，数据还与之前研究的包含25名婴儿和幼儿（年龄6 - 18个月）的数据集进行了整合。一个二房室模型描述了综合数据集。R（+）异构体的群体估计值为（%CV）：中央分布容积1130（10%）ml，外周分布容积626（25%）ml，中央室清除率7.40（8%）ml·min⁻¹。S（-）异构体的分别为1930（15%）ml，�19（58%）ml，和39.5（13%）ml·min⁻¹。典型消除半衰期分别为191分钟和33分钟。随着年龄和体重增加，清除率和中央容积有增加趋势。基础模型表明S（-）异构体的清除率与年龄弱相关；然而，当模型加入体型调整后，没有协变量具有显著性。安全性评估显示，各组间肾功能或肝功能检查、手术引流液量或持续血氧饱和度均无变化。累积吗啡给药量显示患者间差异较大，且各组间无差异。
结论
婴儿（2 - 6个月）中酮咯酸的立体异构体特异性清除率显示，镇痛性S（-）异构体的消除速度较快，这与6 - 18个月婴儿的情况一致。单次静脉注射酮咯酸剂量后未见不良反应。
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