Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations

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From: Clinical Pharmacokinetics(Vol. 45, Issue 11)
Publisher: Wolters Kluwer Health, Inc.
Document Type: Article
Length: 11,715 words
Lexile Measure: 1670L

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Abstract :

The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution ([V.sub.d]) may be altered in children. Hydrophilic drugs with a high [V.sub.d] in adults should be normalised to bodyweight in young children (age In the first 2 years of life, the renal excretion rate should be determined by markers of renal function, such as serum creatinine and p-aminohippuric acid clearance. A dosage guideline for drugs that are significantly excreted by the kidney should be based on the determination of renal function in first 2 years of life. After maturation, the dose should be normalised to BSA. These guidelines are intended to be used in clinical practice and to form a basis for more research. The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study.

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Source Citation   

Gale Document Number: GALE|A199865876