Impacts of Allometric Scaling on the Pharmacokinetics of Morphine in Neonates with HIE
Start Date
April 2025
Location
2nd floor - Library
Abstract
Hypoxic ischemic encephalopathy is a condition where a neonate’s brain is deprived of oxygen during birth resulting in swelling and severe permanent brain damage if not treated. The neonates’ swollen brains are treated using therapeutic hypothermic chambers and kept sedated using morphine. Morphine and hypothermic chambers in combination enhance effectiveness of treatment and recovery in these patients. However, hypoxia alters the clearance of morphine. Understanding morphine pharmacokinetics is integral to dosing these neonates. We investigated the impact of allometric scaling on a population pharmacokinetic model of morphine in hypothermic neonates to determine if dosing regiments need to be changed to ensure optimal dosing. This is a commonly used practice in pediatric pharmacokinetic modeling due to the relative size of pediatric population compared to their adult counterparts. In developing a pharmacokinetic model for the dosing of morphine in a study of neonates being treated for HIE, the allometric scaling values of 0.75 for clearance and 1 for volume were discovered to be potentially lower than the actual volume and clearance value seen in the sample population. The adjustment of the values of clearance and volume to 1.67 and 1.77 (determined using a maximum likelihood function) respectively allowed for a statistically significant improvement in model fit. The results of a sensitivity test show changes in allometric scaling numbers impact clearance and volume of distribution of the drug which may impact future dosing recommendations.
Impacts of Allometric Scaling on the Pharmacokinetics of Morphine in Neonates with HIE
2nd floor - Library
Hypoxic ischemic encephalopathy is a condition where a neonate’s brain is deprived of oxygen during birth resulting in swelling and severe permanent brain damage if not treated. The neonates’ swollen brains are treated using therapeutic hypothermic chambers and kept sedated using morphine. Morphine and hypothermic chambers in combination enhance effectiveness of treatment and recovery in these patients. However, hypoxia alters the clearance of morphine. Understanding morphine pharmacokinetics is integral to dosing these neonates. We investigated the impact of allometric scaling on a population pharmacokinetic model of morphine in hypothermic neonates to determine if dosing regiments need to be changed to ensure optimal dosing. This is a commonly used practice in pediatric pharmacokinetic modeling due to the relative size of pediatric population compared to their adult counterparts. In developing a pharmacokinetic model for the dosing of morphine in a study of neonates being treated for HIE, the allometric scaling values of 0.75 for clearance and 1 for volume were discovered to be potentially lower than the actual volume and clearance value seen in the sample population. The adjustment of the values of clearance and volume to 1.67 and 1.77 (determined using a maximum likelihood function) respectively allowed for a statistically significant improvement in model fit. The results of a sensitivity test show changes in allometric scaling numbers impact clearance and volume of distribution of the drug which may impact future dosing recommendations.
