van Ganzewinkel C, Derijks L, Anand K J S, van Lingen R A, Neef C, Kramer B W, Andriessen P
Division of Neonatology, Department of Pediatrics, Máxima Medical Centre, Veldhoven, The Netherlands.
Acta Paediatr. 2014 Jun;103(6):612-7. doi: 10.1111/apa.12638. Epub 2014 Apr 15.
The therapeutic options available to treat neonatal pain are limited, and one alternative for nonopioid systemic treatment is paracetamol. However, pharmacokinetic data from prolonged administration of intravenous paracetamol in neonates are limited. The aim of this study was to present pharmacokinetics after multiple dose of intravenous paracetamol in very preterm infants of <32 weeks' gestation.
Fifteen very preterm infants received five, six-hourly doses of intravenous paracetamol (7.5 mg/kg). Blood samples were taken to measure paracetamol, glutathione and hepatic function, together with urine samples for paracetamol metabolites.
A two-compartment pharmacokinetic model gave the best fit for all individual patients and resulted in a predictable pharmacokinetic profile. The estimated pharmacokinetic population parameters were volume of distribution 0.764 ± 0.225 L/kg, elimination rate constant (ke ) 0.117 ± 0.091/h and intercompartment rate constants k12 0.607 ± 0.734/h and k21 1.105 ± 0.762/h.
Our study found that multiple doses of intravenous paracetamol resulted in a predictable pharmacokinetic profile in very preterm infants. Increases in postmenstrual age and weight were associated with increased clearance. No evidence of hepatotoxicity was found.
治疗新生儿疼痛的可用治疗选择有限，对乙酰氨基酚是非阿片类全身治疗的一种替代药物。然而，关于新生儿长期静脉注射对乙酰氨基酚的药代动力学数据有限。本研究的目的是呈现孕龄小于32周的极早产儿多次静脉注射对乙酰氨基酚后的药代动力学情况。
15名极早产儿每6小时接受一次静脉注射对乙酰氨基酚（7.5毫克/千克），共注射5次。采集血样以测量对乙酰氨基酚、谷胱甘肽和肝功能，同时采集尿样检测对乙酰氨基酚代谢物。
二室药代动力学模型最适合所有个体患者，得出了可预测的药代动力学曲线。估计的药代动力学总体参数为分布容积0.764±0.225升/千克，消除速率常数（ke）0.117±0.091/小时，室间速率常数k12 0.607±0.734/小时和k21 1.105±0.762/小时。
我们的研究发现，多次静脉注射对乙酰氨基酚在极早产儿中产生了可预测的药代动力学曲线。孕龄和体重的增加与清除率增加相关。未发现肝毒性证据。
