Journal of magnetic resonance imaging : JMRI · 2026
Pharmacokinetics and Pharmacodynamics of a Single Oral Dose of Ascelia-Manganese-Based MRI Contrast Agent (ACE-MBCA) in Adult Subjects With and Without Hepatic Impairment.
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Singal Amit G, Lawitz Eric, Norlin Andreas, Hettiarachchige Nadilka, Bengtsson Thomas, Taouli Bachir
Аннотация
BACKGROUND: Orally administered Ascelia-manganese-based contrast agent (ACE-MBCA) is used for liver MRI, but its feasibility in patients with hepatic dysfunction remains unknown.
PURPOSE: To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of ACE-MBCA in subjects without/with hepatic impairment.
STUDY TYPE: Prospective, open-label, sequential-cohort study.
POPULATION: Thirty-five participants (mean age 56.5 years): 13 with normal hepatic function and 22 with liver disease, consisting of Child-Pugh class A (n = 9), B (n = 6), and C (n = 7).
FIELD STRENGTH/SEQUENCE: 1.5 T, pre- and post-contrast T1-weighted gradient recalled-echo.
ASSESSMENT: Liver signal intensity (SI) was measured on pre- and post-contrast T1-weighted images acquired 1, 4, 8, and 24 h after ACE-MBCA administration. PK assessments included measured manganese concentrations in blood, plasma, urine, and feces over 72 h. PK parameters included AUC, Cmax, and Tmax. Adverse events were reported.
STATISTICAL TESTS: Non-compartmental analysis was performed for PK parameters. Log-transformed AUC and Cmax were compared using ANOVA. Changes in liver SI enhancement were analyzed using a mixed model. Significance was set at p ≤ 0.05.
RESULTS: Tmax of manganese in blood ranged from 0.625 to 3.50 h. Cmax was 44.4 ng/mL in Child-Pugh class C compared to 5.77 ng/mL in the normal group. Cmax increased by 25%-29% in normal/class A and 58%-61% in class B/C. AUC0-24. It increased progressively with hepatic impairment, ranging from 38.4 h × ng/mL (normal) to 320 h × ng/mL (severe impairment). Liver SI peaked at 4 h and was significantly different among normal, mild, moderate, and severe hepatic impairment (45.8%, 35.1%, 18.9%, and 18.4%, respectively), while no difference was observed at 24 h (p = 0.343). Mild to moderate gastrointestinal disorders were reported.
DATA CONCLUSION: Peak liver enhancement occurred 4 h after a single oral dose of ACE-MBCA in all groups, but its magnitude decreased and circulating manganese exposure increased with worsening hepatic function. The single dose of ACE-MBCA was well tolerated.
EVIDENCE LEVEL: 2.
TECHNICAL EFFICACY: 1.
PURPOSE: To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of ACE-MBCA in subjects without/with hepatic impairment.
STUDY TYPE: Prospective, open-label, sequential-cohort study.
POPULATION: Thirty-five participants (mean age 56.5 years): 13 with normal hepatic function and 22 with liver disease, consisting of Child-Pugh class A (n = 9), B (n = 6), and C (n = 7).
FIELD STRENGTH/SEQUENCE: 1.5 T, pre- and post-contrast T1-weighted gradient recalled-echo.
ASSESSMENT: Liver signal intensity (SI) was measured on pre- and post-contrast T1-weighted images acquired 1, 4, 8, and 24 h after ACE-MBCA administration. PK assessments included measured manganese concentrations in blood, plasma, urine, and feces over 72 h. PK parameters included AUC, Cmax, and Tmax. Adverse events were reported.
STATISTICAL TESTS: Non-compartmental analysis was performed for PK parameters. Log-transformed AUC and Cmax were compared using ANOVA. Changes in liver SI enhancement were analyzed using a mixed model. Significance was set at p ≤ 0.05.
RESULTS: Tmax of manganese in blood ranged from 0.625 to 3.50 h. Cmax was 44.4 ng/mL in Child-Pugh class C compared to 5.77 ng/mL in the normal group. Cmax increased by 25%-29% in normal/class A and 58%-61% in class B/C. AUC0-24. It increased progressively with hepatic impairment, ranging from 38.4 h × ng/mL (normal) to 320 h × ng/mL (severe impairment). Liver SI peaked at 4 h and was significantly different among normal, mild, moderate, and severe hepatic impairment (45.8%, 35.1%, 18.9%, and 18.4%, respectively), while no difference was observed at 24 h (p = 0.343). Mild to moderate gastrointestinal disorders were reported.
DATA CONCLUSION: Peak liver enhancement occurred 4 h after a single oral dose of ACE-MBCA in all groups, but its magnitude decreased and circulating manganese exposure increased with worsening hepatic function. The single dose of ACE-MBCA was well tolerated.
EVIDENCE LEVEL: 2.
TECHNICAL EFFICACY: 1.