Scaling adult doses of antifungal and antibacterial agents to children

Antimicrob Agents Chemother. 2012 Jun;56(6):2948-58. doi: 10.1128/AAC.05307-11. Epub 2012 Mar 26.

Abstract

My general pharmacokinetic scaling theory is discussed for the important matter of determining pediatric dosing for existing and new therapeutic drugs when optimal, or near-optimal, dosing for adults is known. The basis for the scaling is the requirement of a time-scaled likeness of the free-drug concentration time histories of children and adults. Broad categories of single and periodic dosing are considered. The former involves the scaling of dosage, and the latter involves both the dosage and schedule. The validity of the scaling relations is demonstrated by using measurements from previously reported clinical trials with adults and children (with ages generally 1 year or older) for the relatively new antifungal agent caspofungin and for the relatively new antibacterial agent linezolid. Standard pharmacodynamic effectiveness criteria are shown to be satisfied for the scaled dosage and schedule for children to the same extent that they are for the referenced adult. Consideration of scaling from adults to children is discussed for the case of new agents where no pediatric data are available and needed parameters are determined from in vitro measurements and preclinical animal data. A connection is also made between the allometric representation of clearance data and the dosing formulas. Limitations of the scaling results for infants because of growth and maturational matters are discussed. The general conclusion from this work is that the scaling theory does indeed have application to pediatric dosing for children, for both confirmation and refinement of present practice and guidance in pediatric treatment with new therapeutic agents.

MeSH terms

  • Acetamides / administration & dosage
  • Adolescent
  • Anti-Bacterial Agents / administration & dosage*
  • Antifungal Agents / administration & dosage*
  • Caspofungin
  • Child
  • Drug Administration Schedule
  • Echinocandins / administration & dosage
  • Female
  • Humans
  • Infant
  • Linezolid
  • Lipopeptides
  • Male
  • Models, Theoretical
  • Oxazolidinones / administration & dosage
  • Young Adult

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • Antifungal Agents
  • Echinocandins
  • Lipopeptides
  • Oxazolidinones
  • Caspofungin
  • Linezolid