ABSTRACT
RATIONALE AND OBJECTIVES: To characterize the pharmacokinetics of gadolinium and to evaluate the safety of gadobenate dimeglumine (Gd-BOPTA) compared with placebo, in subjects with impaired liver function. METHODS: Volunteer adult subjects with hepatic impairment (Child-Pugh classification B or C) received, randomly and in double-blind fashion, either 0.1 mmol/kg gadobenate dimeglumine (n = 11) or placebo (n = 5) by intravenous injection. Blood and urine gadolinium concentrations were determined by ICP-AES and data were analyzed by compartmental and noncompartmental modeling. A full safety evaluation was performed. No magnetic resonance imaging was performed. RESULTS: A bi-exponential model fit the gadolinium blood concentration-time data for 10 of 11 subjects administered Gd-BOPTA. The mean (CV%) distribution and elimination half-lives for these subjects were 0.18 (71.9) and 2.18 (44.2) hours, respectively. Non-parametric analysis of all 11 subjects revealed a mean (CV%) area under the curve [0-inf] of 138 (41.9) microg(Gd).h/mL. Mean (CV%) values for blood clearance, steady-state volume of distribution, and renal clearance were 172 (36.0) mL/minute, 22.9 (16.7) L, and 142 (49.0) mL/minute, respectively. A mean (CV%) of approximately 80% (24.5) of the administered dose was excreted in urine during 60 to 72 hours. No safety concerns were apparent. CONCLUSION: Hepatic impairment did not modify the pharmacokinetics of gadobenate dimeglumine compared with values reported elsewhere for healthy subjects. The contrast agent was well tolerated and safe with an overall incidence of adverse events comparable to that of placebo.
