Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years

Abstract

Objectives: The aim of this study was to evaluate the pharmacokinetic (PK) profile, safety, and efficacy of gadopiclenol, a new high-relaxivity gadolinium-based contrast agent, in children aged 2 to 17 years.

Materials and methods: Children scheduled to undergo contrast-enhanced magnetic resonance imaging of the central nervous system (CNS cohort) or other organs (body cohort) were included sequentially into 3 age groups (12-17, 7-11, and 2-6 years). Gadopiclenol was administered at the dose of 0.05 mmol/kg. A sparse sampling approach was applied, with 4 blood samples per child collected up to 8 hours postinjection. Population PK modeling was used for the analysis, including the CNS cohort and adult subjects from a previous study. Adverse events were recorded, and efficacy was assessed for all children.

Results: Eighty children were included, 60 in the CNS cohort and 20 in the body cohort. The 2-compartment model with linear elimination from the central compartment developed in adults was also suitable for children. Pharmacokinetic parameters were very similar between adults and children. Terminal elimination half-life was 1.82 hours for adults and 1.77 to 1.29 hours for age groups 12-17 to 2-6 years. The median clearance ranged from 0.08 L/h/kg in adults and 12-17 years to 0.12 L/h/kg in 2-6 years. The median central and peripheral volumes of distribution were 0.11 to 0.12 L/kg and 0.06 L/kg, respectively, for both adults and children. Simulations of plasma concentrations showed minor differences, and median area under the curve was 590 mg·h/L for adults and 582 to 403 mg·h/L for children. Two patients (2.5%) experienced nonserious adverse events considered related to gadopiclenol: a mild QT interval prolongation and a moderate maculopapular rash. Despite the limited number of patients, this study showed that gadopiclenol improved lesion detection, visualization, and diagnostic confidence.

Conclusions: The PK profile of gadopiclenol in children aged 2 to 17 years was similar to that observed in adults. Thus, there is no indication for age-based dose adaptation, and comparable plasma gadopiclenol concentrations are predicted to be achieved with body weight-based dosing in this population. Gadopiclenol at 0.05 mmol/kg seems to have a good safety profile in these patients and could improve lesion detection and visualization, therefore providing better diagnostic confidence.

Trial registration: ClinicalTrials.gov NCT03749252.

Conflict of interest statement

Conflicts of interest and sources of funding: The authors have no conflicts of interest to declare. This study was funded by Guerbet.

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.

Figures

FIGURE 1

Individual and median gadopiclenol plasma concentrations over time by age group. Individual gadopiclenol plasma concentrations indicated in blue are profiles incompatible with an intravenous administration, and in orange and red are profiles with very high initial gadopiclenol plasma concentration incompatible with the administered dose divided by the theoretical blood (orange) and plasma volume (red).

FIGURE 2

Simulated gadopiclenol plasma concentrations and AUCinf by age group. In the box plot, the solid line is the median, the end of the “box” are the first and third quartile. The whiskers show the lowest value still within 1.5 interquartile range (IQR) of the lower quartile, and the highest value still within 1.5 IQR of the upper quartile. Data values that do not fall between the whiskers are plotted as outliers (markers outside of the whiskers).