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Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children

Sophida Boonsathorn1,2, Iek Cheng3, Frank Kloprogge4

  • 1Infection, Inflammation, Immunity Section, Room 661, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London, WC1N 1EH, UK.

Clinical Pharmacokinetics
|April 22, 2018
PubMed

Insights

This study analyzed posaconazole pharmacokinetics in children. Posaconazole suspension bioavailability was reduced in children with diarrhea or taking proton pump inhibitors, impacting treatment efficacy.

Area of Science:

  • Pharmacology
  • Pediatric Medicine
  • Drug Development

Background:

  • Posaconazole is an antifungal medication used in immunocompromised patients.
  • Understanding its pharmacokinetics in children is crucial for effective dosing.
  • Previous studies have limited data on pediatric posaconazole pharmacokinetics.

Purpose of the Study:

  • To investigate the population pharmacokinetics of posaconazole in immunocompromised children.
  • To assess how patient characteristics influence posaconazole exposure.
  • To simulate optimal starting doses for pediatric patients.

Main Methods:

  • Population pharmacokinetic analysis of posaconazole plasma concentrations from 117 children.
  • Utilized a one-compartment model with allometric scaling.
  • Investigated effects of tablet vs. suspension, dose, diarrhea, and proton pump inhibitors.

Main Results:

  • A total of 338 posaconazole plasma concentrations were analyzed.
  • Suspension bioavailability decreased with increasing dose.
  • Diarrhea and proton pump inhibitors were associated with reduced suspension bioavailability.

Conclusions:

  • This is the largest pediatric population pharmacokinetic study of posaconazole.
  • Covariate effects were similar to adults, but suspension bioavailability is a concern.
  • Reduced bioavailability in specific patient groups may limit posaconazole's use.
Abstract

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