PK of Clindamycin and Trimethoprim-sulfamethoxazole in Infants and Children
Status:
Completed
Trial end date:
2020-06-30
Target enrollment:
Participant gender:
Summary
Developmental changes in physiology during childhood influence drug dosing. Failure to
account for these changes leads to improper dosing, which is associated with decreased drug
efficacy and safety in children. Population physiologically-based pharmacokinetic (PBPK)
modeling offers the opportunity to predict optimal drug dosing based on physiologic
parameters adjusted for developmental changes.
PBPK models are mathematical constructs that incorporate physiologic processes with drug
characteristics and genetic variances to characterize the dose-exposure relationship across
the age continuum. These models integrate drug-specific (e.g., metabolism, protein binding)
and systems-specific (e.g., organ size, blood flow) information to predict the effect of
different factors (e.g., age, genetic variants, disease) on drug exposure. By accounting for
these factors and using data from clinical trials to confirm the modeling, PBPK models can
reduce the number of children needed for clinical trials while maximizing dose-based efficacy
and safety.
This trial will evaluate a platform to prospectively validate population PBPK models in
children. The study drugs, clindamycin and Bactrim (aka TMP-SMX), are ideal candidates to
evaluate population PBPK models in children due to their differing physico-chemical
properties and elimination pathways. In addition, a trial of clindamycin and TMP-SMX has
broad clinical applicability, as both drugs are among the most commonly used agents to treat
gram-positive infections in infants and children.
Phase:
Phase 1
Details
Lead Sponsor:
Michael Cohen-Wolkowiez
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)