Kearns G L, Reed M D
Division of Pediatric Infectious Disease, Clinical Pharmacology (Arkansas Children's Hospital), Little Rock.
Clin Pharmacokinet. 1989;17 Suppl 1:29-67. doi: 10.2165/00003088-198900171-00005.
A significant increase in the knowledge base in paediatric clinical pharmacology has occurred over the past 2 decades and has largely been the result of important scientific and sociological advancements pertaining to paediatric therapeutics. Although the data on drug disposition in infants and children have increased considerably over the past few years, pharmacokinetic-pharmacodynamic interactions, particularly the effect of development on pharmacodynamics, remain poorly understood. The impact of developmental physiology on drug absorption, distribution, metabolism and elimination in infants and children is reviewed and contrasted to the determinants of clinical pharmacokinetics in neonates. The most notable differences in drug disposition between infants and children when compared with neonates and young adults centre around alterations in body water and serum protein composition and the affinity/capacity for hepatic biotransformation of xenobiotics. As opposed to examining the effect of age on the disposition of specific compounds, the differences in developmental pharmacology are highlighted by the review of important and/or emerging pharmacokinetic-pharmacodynamic controversies in infants and children. These include the issues of altered drug distribution and metabolism in cystic fibrosis, pharmacokinetic determinants of successful antimicrobial therapy in bacterial meningitis and the pharmacokinetic determinants of immunosuppression treatment with cyclosporin. The pharmacological differences which are characteristic of development in both infants and children are also reviewed by examination of considerations for clinical pharmacokinetic evaluations such as specific routes and techniques for both drug administration and determination of sampling strategies. Clinical pharmacokinetics will continue to function as a bridge between the generation of new information and the practical application of this knowledge. Consequently, pharmacokinetics provides a pharmacological tool for use in research and clinical care. The clinical application of this tool is examined by a review of the pertinent assumptions and limitations, as well as useful mathematical techniques for use in paediatric patients. Additionally, 'non-traditional' uses of clinical pharmacokinetics (forensic application and use to evaluate organ function) in infants and children are discussed as are considerations for research use of clinical pharmacokinetic data.
在过去20年里，儿科临床药理学的知识库有了显著增长，这在很大程度上是与儿科治疗学相关的重要科学和社会学进步的结果。尽管过去几年关于婴儿和儿童药物处置的数据有了大幅增加，但药代动力学-药效学相互作用，尤其是发育对药效学的影响，仍知之甚少。本文综述了发育生理学对婴儿和儿童药物吸收、分布、代谢和排泄的影响，并与新生儿临床药代动力学的决定因素进行了对比。与新生儿和年轻人相比，婴儿和儿童药物处置最显著的差异集中在身体水分和血清蛋白组成的变化以及肝脏对外源化合物生物转化的亲和力/能力上。与研究年龄对特定化合物处置的影响不同，本文通过回顾婴儿和儿童重要的和/或新出现的药代动力学-药效学争议，突出了发育药理学的差异。这些争议包括囊性纤维化中药物分布和代谢的改变、细菌性脑膜炎中成功抗菌治疗的药代动力学决定因素以及环孢素免疫抑制治疗的药代动力学决定因素。还通过审查临床药代动力学评估的注意事项，如药物给药的具体途径和技术以及采样策略的确定，综述了婴儿和儿童发育所特有的药理学差异。临床药代动力学将继续作为新信息产生与该知识实际应用之间的桥梁。因此，药代动力学提供了一种用于研究和临床护理的药理学工具。本文通过回顾相关假设和局限性以及用于儿科患者的有用数学技术，研究了该工具的临床应用。此外，还讨论了临床药代动力学在婴儿和儿童中的“非传统”用途（法医应用和用于评估器官功能）以及临床药代动力学数据研究用途的注意事项。
