Population pharmacokinetics of naloxegol in paediatric subjects receiving opioids

Abstract

Abstract Purpose To characterize the pharmacokinetics (PK) of naloxegol in paediatric subjects (≥ 6 months to <18 years of age) who are either with or at risk of developing opioid-induced constipation (OIC) following single dose administration. Methods Subjects in three age groups (≥12 to <18 years [adolescents], ≥6 to <12 years, and ≥6 months to <6 years) received at least one low or high dose of naloxegol estimated to achieve plasma exposures comparable to adult 12.5 mg or 25 mg doses, respectively. Plasma naloxegol concentrations were used to estimate PK parameters using non-compartmental (NCA; ≥6 to <18 years) and Population PK (PPK; ≥6 months to < 18 years of age) analyses. The PPK model was developed using previously collected adult data and paediatric data from the current study. Results Naloxegol exhibits comparable PK characteristics in paediatric and adult subjects. Neither age nor body weight was identified as a significant covariate in the prior (adult only data), or current model. Naloxegol NCA- and PPK-derived AUC0–∞ values normalized to the adult 12.5 mg or 25 mg dose in the ≥6 to <12 years and ≥12 to <18 years age groups were comparable to adults. PPK model-predicted naloxegol AUC0–∞ values for the 25 mg adult equivalent dose for all paediatric age groups were comparable to adults. Conclusion The PK of naloxegol was well characterized in paediatric subjects ≥ 6 months of age utilizing both NCA and PPK analysis and was shown to be comparable to adult subjects.