Krekels Elke H J, Tibboel Dick, Knibbe Catherijne A J
a 1 Leiden University, Leiden Academic Center for Drug Research, Division of Pharmacology , Leiden, The Netherlands.
b 2 Erasmus MC - Sophia Children's Hospital, Intensive Care and Department of Pediatric Surgery , Rotterdam, The Netherlands.
Expert Opin Drug Metab Toxicol. 2015;11(11):1679-82. doi: 10.1517/17425255.2015.1065815. Epub 2015 Jul 13.
Interest in pediatric pharmacology has increased over the past two decades. With few exceptions, research efforts are currently, however, still limited to pharmacokinetic (PK) queries on single drugs in a limited number of subjects. It is now time to move forward and integrate and generalize the PK information that is currently available more efficiently across different drugs and different populations. Additionally, for pediatric patients to truly benefit from pharmacological research efforts, the knowledge that is obtained in these studies needs to be translated into dosing recommendations that are subsequently prospectively evaluated in adequately powered randomized clinical trials. Finally, as drug effects and safety are the result of both PK and pharmacodynamic (PD) processes and as developmental changes may occur in both processes, it is essential for PK studies to be followed-up by PD studies when dose-adjustments based on PKs alone have been proven insufficient. In this report, examples illustrating this approach are provided. As PD studies in children are generally more complicated to perform than PK studies, this is where a big challenge in pediatric pharmacological research still lies.
在过去二十年里,对儿科药理学的关注有所增加。然而,目前除了少数例外情况,研究工作仍局限于对有限数量受试者的单一药物进行药代动力学(PK)研究。现在是时候向前迈进,更有效地整合和归纳目前在不同药物和不同人群中可获得的PK信息了。此外,为了让儿科患者真正从药理学研究工作中受益,这些研究中获得的知识需要转化为给药建议,随后在有足够样本量的随机临床试验中进行前瞻性评估。最后,由于药物效应和安全性是PK和药效学(PD)过程共同作用的结果,且这两个过程都可能发生发育变化,因此当仅基于PK进行剂量调整已被证明不足时,PK研究之后进行PD研究至关重要。在本报告中,提供了说明这种方法的示例。由于儿童的PD研究通常比PK研究更复杂,这仍是儿科药理学研究中的一大挑战所在。