El-Tahtawy Ahmed, Kokki Hannu, Reidenberg Bruce E
Metrum Research Group, Tariffville, CT, USA.
J Clin Pharmacol. 2006 Apr;46(4):433-42. doi: 10.1177/0091270006286433.
Young children are often undertreated for pain. One barrier to effective pain treatment is understanding the pharmacokinetic behavior of analgesics in this age group. Oxycodone is a commonly prescribed opioid for severe pain, yet little is known about its pharmacokinetics in young children. This article used population pharmacokinetic modeling to synthesize pharmacokinetic data from several studies into a model. A single population model that described the observed pharmacokinetics was developed. The combined data were best described with a 2-compartment linear model with different first-order absorption rates depending on route of administration. Weight was found to significantly influence both clearance (CL) and volume of distribution (Vd). The following model adequately describes the population pharmacokinetic profile of oxycodone where absolute bioavailability (F) is estimated for each administration route: CL/F=55x(body weight/70)0.87; V/F=86x(body weight/70)1.16. The interindividual coefficients of variation in CL and Vd were 20.2 and 19.7%, respectively. This finding confirms that the allometric scaling using the above model explained most of the variability in exposure observed among children. This model confirms using a weight-based dose for oxycodone without adjustment for age between 6 months and 7 years and is valuable for evaluating dosing schedules and dosing routes.
幼儿的疼痛常常得不到充分治疗。有效疼痛治疗的一个障碍是了解该年龄组镇痛药的药代动力学行为。羟考酮是一种常用于治疗重度疼痛的阿片类药物,但对其在幼儿中的药代动力学了解甚少。本文使用群体药代动力学建模将多项研究的药代动力学数据综合成一个模型。开发了一个描述观察到的药代动力学的单一群体模型。联合数据用一个二室线性模型能得到最佳描述,该模型根据给药途径有不同的一级吸收速率。发现体重对清除率(CL)和分布容积(Vd)均有显著影响。以下模型充分描述了羟考酮的群体药代动力学特征,其中为每种给药途径估计了绝对生物利用度(F):CL/F = 55×(体重/70)^0.87;V/F = 86×(体重/70)^1.16。CL和Vd的个体间变异系数分别为20.2%和19.7%。这一发现证实,使用上述模型进行异速生长标度解释了儿童中观察到的大部分暴露变异性。该模型证实,对于6个月至7岁的儿童,羟考酮可采用基于体重的剂量,无需根据年龄进行调整,这对于评估给药方案和给药途径很有价值。