Division of Pediatric Infectious Diseases and Laboratory of Applied Pharmacokinetics, University of Southern California, Los Angeles, California, USA.
Clin Pharmacokinet. 2011 Mar;50(3):143-89. doi: 10.2165/11539260-000000000-00000.
There are over 2.1 million HIV-infected children worldwide, who are increasingly exposed to antiretroviral therapy. Given the enormous physiological changes associated with maturation, the role of individualized therapy and optimal dosing in children and adolescents is likely different than in adults. This review summarizes the pharmacodynamics, pharmacokinetics and pharmacogenomics of antiretroviral therapy in children and adolescents, and it discusses the roles of these in the optimization of therapy through the practice of therapeutic drug monitoring/management. Within the pharmacodynamics section are tables and discussion about what is known of the relationships between drug concentrations, inhibitory quotients and effects - both desired and toxic. The pharmacokinetics section summarizes all reported antiretroviral pharmacokinetic data in children, divided into data from population and non-population analytic approaches. Measures of interindividual pharmacokinetic variability are reported. Sampling strategies for the measurement and the interpretation of plasma antiretroviral drug concentrations are suggested, as well as dosing with degrees of renal or hepatic failure. Relevant pharmacogenomic polymorphisms are summarized, and the role for pharmacogenomics testing is discussed. Incorporation of dose adjustment on the basis of measured serum drug concentrations is reviewed, including all such paediatric experience reported in the literature. Discussion of the influences of malnutrition and herbal remedies is also included. Finally, consideration is given to future work in this field.
全世界有超过 210 万感染 HIV 的儿童，他们越来越多地接触到抗逆转录病毒疗法。鉴于与成熟相关的巨大生理变化，儿童和青少年个体化治疗和最佳剂量的作用可能与成人不同。这篇综述总结了抗逆转录病毒治疗在儿童和青少年中的药效学、药代动力学和药物基因组学，并讨论了通过治疗药物监测/管理实践优化治疗的作用。在药效学部分，有表格和讨论，介绍了药物浓度、抑制率和效果（包括所需效果和毒性）之间关系的已知情况。药代动力学部分总结了所有在儿童中报告的抗逆转录病毒药代动力学数据，分为来自群体和非群体分析方法的数据。报告了个体间药代动力学变异性的衡量标准。提出了测量和解释血浆抗逆转录病毒药物浓度的采样策略，以及在肾功能或肝功能衰竭时的剂量调整。总结了相关的药物基因组学多态性，并讨论了药物基因组学检测的作用。根据测量的血清药物浓度进行剂量调整的情况进行了综述，包括文献中报告的所有此类儿科经验。还讨论了营养不良和草药的影响。最后，考虑了该领域未来的工作。
