Population Pharmacokinetics of Naloxegol in Pediatric Subjects Receiving Opioids

Area of Science:

• Pharmacology
• Pediatric Medicine
• Gastroenterology

Background:

• Opioid-induced constipation (OIC) is a common side effect of opioid therapy.
• Naloxegol is a peripherally acting mu-opioid receptor antagonist used to treat OIC.
• Pediatric PK data are essential for safe and effective drug use in children.

Purpose of the Study:

• To characterize the pharmacokinetics (PK) of naloxegol in pediatric subjects aged 6 months to 18 years.
• To assess if age or body weight significantly impacts naloxegol PK in this population.
• To compare pediatric naloxegol PK with previously established adult data.

Main Methods:

• Single oral dose administration of naloxegol to pediatric subjects in age-stratified groups.
• Collection of intensive and sparse plasma samples for naloxegol concentration analysis.
• Population PK analysis combining pediatric and adult data, using a 2-compartment model with Weibull absorption.

Main Results:

• Naloxegol PK exhibited linear characteristics across the studied dose range.
• Neither age nor body weight were identified as significant covariates affecting naloxegol PK.
• PK exposures in pediatric groups aged 12 months to 18 years were comparable to adult equivalent doses.
• The youngest pediatric group (6 months to <12 years) showed approximately 80% lower PK estimates compared to adults.

Conclusions:

• Naloxegol demonstrates predictable and linear PK in pediatric patients aged 6 months and older.
• PK characteristics are generally comparable between pediatric and adult populations.
• The findings support the potential for age-appropriate dosing of naloxegol in children for OIC management.