Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Radboud University Medical Center, Amalia Children's Hospital, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands.
Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands.
Pediatr Nephrol. 2020 Jul;35(7):1153-1172. doi: 10.1007/s00467-019-04304-9. Epub 2019 Aug 2.
In children, the main causes of chronic kidney disease (CKD) are congenital diseases and glomerular disorders. CKD is associated with multiple physiological changes and may therefore influence various pharmacokinetic (PK) parameters. A well-known consequence of CKD on pharmacokinetics is a reduction in renal clearance due to a decrease in the glomerular filtration rate. The impact of renal impairment on pharmacokinetics is, however, not limited to a decreased elimination of drugs excreted by the kidney. In fact, renal dysfunction may lead to modifications in absorption, distribution, transport, and metabolism as well. Currently, insufficient evidence is available to guide dosing decisions on many commonly used drugs. Moreover, the impact of maturation on drug disposition and action should be taken into account when selecting and dosing drugs in the pediatric population. Clinicians should take PK changes into consideration when selecting and dosing drugs in pediatric CKD patients in order to avoid toxicity and increase efficiency of drugs in this population. The aim of this review is to summarize known PK changes in relation to CKD and to extrapolate available knowledge to the pediatric CKD population to provide guidance for clinical practice.
在儿童中，慢性肾脏病（CKD）的主要病因是先天性疾病和肾小球疾病。CKD 与多种生理变化相关，因此可能影响各种药代动力学（PK）参数。众所周知，CKD 对 PK 的影响是由于肾小球滤过率降低导致肾脏清除率降低。然而，肾功能不全对 PK 的影响不仅限于减少肾脏排泄的药物的消除。事实上，肾功能障碍可能导致吸收、分布、转运和代谢的改变。目前，对于许多常用药物，尚无足够的证据来指导剂量决策。此外，在选择和给儿童人群用药时，应考虑药物处置和作用的成熟度。为了避免毒性并提高该人群中药物的效率，临床医生应在选择和给患有儿科 CKD 的患者用药时考虑 PK 变化。本文的目的是总结与 CKD 相关的已知 PK 变化，并将现有知识外推至儿科 CKD 人群，为临床实践提供指导。
