Children Are Not Small Adults, but Can We Treat Them As Such?. (28th January 2019)

• Record Type: Journal Article
• Authors: Krekels, Elke H.J.; Calvier, Elisa A.M.; van der Graaf, Piet H.; Knibbe, Catherijne A.J.
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 8:Number 1(2019)
• Page Start: 34
• Page End: 38
• Publication Date: 2019-01-28
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12366
• Languages: English
• ISSNs: 2163-8306

Abstract

Abstract : Although children cannot be considered small adults due to nonlinear processes underlying the pharmacokinetics of drugs, pediatric doses are typically still expressed per kilogram. We use a physiologically based pharmacokinetic (PBPK) workflow to assess the accuracy of linear scaling of plasma clearance (CLp) for hypothetical drugs with ranges of realistic parameter values in pediatric patients of different ages. The results are compared with 0.75 fixed allometric scaling (AS 0.75). Linear CLp scaling is accurate down to the age of 1 month for drugs undergoing glomerular filtration, except when these drugs are highly bound to alpha‐1‐acid glycoprotein (AGP). For hepatically cleared drugs, linear scaling is reasonably accurate down the age of 2 years, except for AGP‐bound drugs with a low extraction ratio and mature isoenzymes. In neonates, linear scaling outperforms AS 0.75 for human serum albumin (HSA) and AGP‐bound drugs excreted through glomerular filtration. These results suggest that pediatric patients can, in many cases, be treated as small adults.