Pharmacokinetic variability in the adolescent: implications of body size and organ function for dosage regimen design.

Pharmacokinetic variability in the adolescent: implications of body size and organ function for dosage regimen design.
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青少年的药代动力学变异性:身体大小和器官功能对剂量方案设计的影响。

DOI:
10.1016/s1054-139x(94)90633-5
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发表时间:
1994
期刊:
The Journal of adolescent health : official publication of the Society for Adolescent Medicine
影响因子:
--
通讯作者:
Rodman,JH
Rodman,JH
中科院分区:
--
文献类型:
--
作者:
Rodman,JH

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虽然有令人信服的临床研究证明成人和儿童患者之间存在重要的药代动力学差异,但调整特定药物剂量的指南通常基于经验和有限的数据。成人剂量通常为儿童治疗提供参考点,并根据体型进行调整。体重和体表面积(BSA)通常用于调整儿科患者的成人剂量,但产生的绝对剂量差异很大。对于5岁的儿童,基于BSA的剂量将比根据体重调整的剂量高50%以上。体重或BSA的选择通常是任意的,并且在儿科患者中评价广泛年龄范围内的药物或比较剂量未以类似方式调整的两种药物时,可能是重要的混杂变量。例如,针对HIV感染的儿科患者的比较试验正在评估通过BSA给药的齐多夫定与通过体重给药的扎西他滨。器官功能随着年龄的变化在儿科患者中,但很少有信息是可用的成熟对肝或肾功能的影响和药物disposition.The使用模型基板的器官功能提供了潜在的阐明器官功能相对于成熟,特别是那些功能的能力与青春期和性别分化的开始。
Although there are convincing clinical studies demonstrating important pharmacokinetic differences between the adult and Pediatric patient, guidelines for adjusting the dosages of specific drugs are often based on empirical and limited data.Adult doses often provide the reference point for therapy in children with adjustment for body size. Both body weight and body surface area (BSA) are commonly used to adjust adult doses for pediatric patients but yield substantially different absolute doses.For the child age five years, the BSA-based dose will be more than 50 percent greater than the dose adjusted for body weight. The choice of weight or BSA is often arbitrary and may be an important confounding variable when evaluating drugs over wide ranges of age in pediatric patients or comparing two drugs for which doses are not adjusted in a similar manner. For example, comparative trials for HIV-infected pediatric patients are evaluating zidovudine dosed by BSA with zalcitabine dosed by body weight. Organ function changes with age in pediatric patients yet little information is available on the effects of maturation on hepatic or renal function and the consequences for drug disposition.The use of model substrates for organ function offers potential for elucidating organ function relative to maturation and, in particular, to those functional capacities associated with the onset of puberty and gender differentiation.
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