A PBPK study combined existing compound models with age-specific physiology, including midazolam and lorazepam. Performance in older children did not guarantee neonatal accuracy.
The approach
Seven drugs with different pharmacokinetic properties were modeled using one software platform. Predictions were compared with observed data using parameter ratios and visual checks.
Overall performance was more favorable in infants, children, and adolescents, while predictive performance tended to decrease in term and preterm neonates.
What acceptance means
A model meeting a selected exposure-error criterion is not proof that every individual dose will be optimal or that clinical effects are accurately predicted. Developmental enzyme function, distribution, and physiology require appropriate assumptions.
The study did not establish interchangeability of all software platforms or measure airway safety and cognitive effects at every predicted concentration. Its practical contribution is a feasible modeling strategy with explicit limits. A neonatal opinion should identify the age range and validation data rather than importing confidence from an adult or older-child model unchanged.
Source paper
Original analysis of the supplied journal article, identified as PMC9651907.
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