Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

Background And Objectives: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 μg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection.

Consistent methods for fat-free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults.

Quantifying the effect of kidney disease on glomerular filtration rate (GFR) is important when describing variability in the clearance of drugs eliminated by the kidney. We aimed to develop a continuous model for renal function (RF) from prematurity to adulthood based on consistent models for fat-free mass (FFM), creatinine production rate (CPR), and GFR. A model for fractional FFM in premature neonates to adults was developed using pooled data from 4462 subjects and 2847 FFM observations.

Predicting weight using postmenstrual age--neonates to adults.

Objectives: To describe the pattern and variability of body weight with postmenstrual age (PMA) using nonlinear mixed effect modeling and to create a single mathematical function that can be used from prematurity to adulthood.

Background: PMA has been shown to predict functional properties of humans such as glomerular filtration rate and drug clearance. Widely used growth charts use postnatal age to predict weight in an idealized population and are not available as a mathematical function.

Pediatric pharmacology in the first year of life.

Purpose Of Review: Toxicity concerns and awareness during anesthesia issues continue to concern pediatric anesthesiologists. Most developmental pharmacokinetic, pharmacodynamic and pharmacogenomic changes occur within the first year of life. Understanding these early changes can improve drug use in this cohort.