单次静脉注射异丙酚的成熟药代动力学。

Maturational pharmacokinetics of single intravenous bolus of propofol.

作者信息

Allegaert Karel, de Hoon Jan, Verbesselt Rene, Naulaers Gunnar, Murat Isabelle

机构信息

Neonatal Intensive Care Unit, University Hospital Gasthuisberg, Leuven, Belgium.

出版信息

Paediatr Anaesth. 2007 Nov;17(11):1028-34. doi: 10.1111/j.1460-9592.2007.02285.x.

DOI:10.1111/j.1460-9592.2007.02285.x

PMID:17897267

Abstract

BACKGROUND

Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children.

METHODS

Newly collected observations following intravenous bolus administration of propofol in preterm and term neonates (n = 9) were compared with earlier reported pharmacokinetic estimates in toddlers and young children. Data are reported by median and range. Mann-Whitney U-test or correlation was used to analyze differences in pharmacokinetic findings between neonates, toddlers and young children.

RESULTS

Concentration-time profiles obtained were interpreted by two-stage analysis as a three compartment open model in nine neonates with a median weight of 2.51 (range 0.91-3.8) kg and a median postmenstrual age (PMA) of 36 (range 27-43) weeks. Median clearance (CL) was 13.6 (range 3.7-78.2) ml.min(-1).kg(-1) and median apparent volume of distribution at steady state (V(ss)) was 3.7 (1.33-7.96) l.kg(-1). Following allometric scaling and standardization to 70 kg, median CL was 442 (range 97-2184) ml.min(-1).70 kg(-1). Compared with earlier reported observations in toddlers and children, median clearance (kg.min(-1)) was significantly lower in neonates (P < 0.01) and these differences remained significant after allometric scaling (70 kg.min(-1)) while V(ss) (l.kg(-1)) was significantly lower in neonates (P < 0.01).

CONCLUSIONS

Propofol disposition is significantly different in neonates compared with toddlers and young children, reflecting both ontogeny and differences in body composition. Based on the reduced clearance of propofol, a longer recovery time is more likely to occur in neonates.

摘要

背景

我们的目的是记录单次静脉推注异丙酚后早产儿和足月儿的药代动力学情况，并将这些估计值与幼儿和儿童的药代动力学研究结果进行比较。

方法

将新收集的早产儿和足月儿（n = 9）静脉推注异丙酚后的观察结果与早期报道的幼儿和儿童药代动力学估计值进行比较。数据以中位数和范围表示。采用曼-惠特尼U检验或相关性分析来分析新生儿、幼儿和儿童药代动力学结果的差异。

结果

对9名体重中位数为2.51（范围0.91 - 3.8）kg、月经后年龄（PMA）中位数为36（范围27 - 43）周的新生儿，通过两阶段分析将获得的浓度-时间曲线解释为三室开放模型。清除率（CL）中位数为13.6（范围3.7 - 78.2）ml·min⁻¹·kg⁻¹，稳态时表观分布容积（V(ss)）中位数为3.7（1.33 - 7.96）l·kg⁻¹。按照体重70 kg进行异速缩放和标准化后，CL中位数为442（范围97 - 2184）ml·min⁻¹·70 kg⁻¹。与早期报道的幼儿和儿童观察结果相比，新生儿的CL中位数（kg·min⁻¹）显著更低（P < 0.01），异速缩放（70 kg·min⁻¹）后这些差异仍然显著，而新生儿的V(ss)（l·kg⁻¹）显著更低（P < 0.01）。