A Comprehensive Overview of the Efficacy and Safety of Gadopiclenol: A New Contrast Agent for MRI of the CNS and Body.

ABSTRACT: This review describes the pharmacokinetics, efficacy, and safety of gadopiclenol, a new macrocyclic gadolinium-based contrast agent (GBCA) recently approved by the Food and Drug Administration at the dose of 0.05 mmol/kg. Gadopiclenol is a high relaxivity contrast agent that shares similar pharmacokinetic characteristics with other macrocyclic GBCAs, including a predominant renal excretion. In pediatric patients aged 2-17 years, the pharmacokinetic parameters (assessed through a population pharmacokinetics model) were comparable to those observed in adults, indicating no need for age-based dose adjustment. For contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) and body indications, gadopiclenol at 0.05 mmol/kg was shown to be noninferior to gadobutrol at 0.1 mmol/kg in terms of 3 lesion visualization parameters (ie, lesion border delineation, internal morphology, and contrast enhancement). Moreover, for contrast-enhanced MRI of the CNS, compared with gadobenate dimeglumine at 0.1 mmol/kg, gadopiclenol exhibited superior contrast-to-noise ratio at 0.1 mmol/kg and comparable contrast-to-noise ratio at 0.05 mmol/kg. A pooled safety analysis of 1047 participants showed a favorable safety profile for gadopiclenol. Comparative studies showed that the incidence and nature of adverse drug reactions with gadopiclenol were comparable to those observed with other GBCAs. Importantly, no significant safety concerns were identified in pediatric and elderly patients, as well as in patients with renal impairment. Overall, these findings support the clinical utility and safety of gadopiclenol for MRI in adult and pediatric patients aged 2 years and older in CNS and body indications.

Pharmacokinetics, Dialysability, and Safety of Gadopiclenol, a New Gadolinium-Based Contrast Agent, in Patients With Impaired Renal Function.

OBJECTIVES: The aims of this study were to evaluate the pharmacokinetics (PK) of gadopiclenol, a new macrocyclic gadolinium based-contrast agent, in subjects with impaired renal function, and to assess its dialysability in subjects with end-stage renal disease (ESRD). METHODS AND MATERIALS: This 2-center, open-label, phase 1 study included 5 successive cohorts of 8 adult subjects: healthy subjects (cohort 1), subjects with mild (cohort 2), moderate (cohort 3), severe (cohort 4) renal impairment, or ESRD (cohort 5), who received a single intravenous injection of gadopiclenol (0.1 mmol/kg). Blood and urine samples were collected at different time points in cohorts 1 to 4, and blood and dialysate samples were collected at each hemodialysis session (4-hour session on day 1, day 3, and day 5) in cohort 5. Gadopiclenol elimination and safety were assessed for up to 6 months. Pharmacokinetics parameters were calculated using noncompartmental analysis. RESULTS: A total of 40 subjects were included, with a mean age of 51.5 years (range, 18-71 years). No significant difference in the mean maximum concentration values and the distribution volume was observed among cohorts 1 to 4. Urinary excretion of unchanged gadopiclenol was delayed with the degree of renal impairment and ranged between 96% and 84% in subjects with mild to severe renal impairment. Compared with that of healthy subjects, the mean area under the plasma concentration curve was 54%, 148%, and 769% higher in subjects with mild, moderate, or severe renal impairment, respectively. The mean terminal half-life was prolonged with the degree of renal impairment (1.9, 3.3, 3.8, and 11.7 hours for cohorts 1-4). In ESRD subjects, gadopiclenol was effectively removed from the plasma (95% to 98%) after the first hemodialysis session. Gadopiclenol concentration in plasma was below the limit of quantification for all subjects after the second hemodialysis session. Gadopiclenol concentration was below limit of quantification in all plasma and urine samples collected at 1, 3, and 6 months. Five subjects (12.5%) experienced adverse events related to gadopiclenol, none serious and all resolved. Laboratory measurements, vital signs, and electrocardiography did not raise any safety concern. CONCLUSIONS: Gadopiclenol elimination half-life was prolonged in subjects with mild to severe renal impairment, yet its renal clearance remains complete or nearly complete. In ESRD subjects, gadopiclenol was effectively removed from the plasma after 1 hemodialysis session, and up to 3 hemodialysis sessions were sufficient to completely clear it. No safety concern was raised. Therefore, no dose adjustment seems necessary in this patient population.