Optimizing Pediatric Dosing: A Developmental Pharmacologic Approach

Gail D. Anderson, Ph.D.; Anne M. Lynn, M.D.

Disclosures

Pharmacotherapy. 2009;29(6):680-690. 

In This Article

Summary of Dosing Recommendations and Limitations of the Data

This review summarizes the evidence that children require substantially higher, weight-corrected doses than adults for drugs metabolized solely by CYP1A2, CYP2C9, or CYP3A4 ( Table 2 ).[11,19,24–29,31,32,34,35,37–39,42–46,50–53,55–61,63–65,67,68,72–75,78–83,85,90,92–111] In contrast, weight-corrected doses for drugs eliminated by renal excretion or metabolism by CYP2C19, CYP2D6, NAT2, or UGTs are similar in children and adults. Prediction of dosing in neonates and infants is difficult because studies have been limited to date.

A limitation of this analysis was the observational nature of the available pharmacokinetic studies. These studies have mainly involved small numbers of children, and only a limited number of drugs have been studied for each metabolic pathway. Many drugs are eliminated by a combination of various pathways and/or are metabolized by isoenzymes other than those of the UGT or CYP families. In the case of multiple pathways, an initial estimation of the effect of age may be possible. Even for drugs that have been on the market for a long time, their pathways of elimination and the specific metabolic enzymes involved may be unknown.

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