RATIONALE AND OBJECTIVES: To determine the safety and pharmacokinetics of gadobenate dimeglumine in a group of subjects with moderate or severe renal impairment. METHODS: The safety and pharmacokinetic profile of gadobenate dimeglumine, a gadolinium (Gd3+) chelate complex in development as a contrast agent for MRI, were evaluated in a placebo-controlled, double-blind, multicenter trial. Subjects with moderate or severe renal impairment (creatinine clearances of 31 to 60 or 10 to 30 mL/min, respectively) received a0.2-mmol/kg intravenous bolus of Gd3+ or saline placebo. Blood samples (up to 72 hours) and urine and fecal samples (up to 216 hours) were assayed for total Gd3+ content by inductively coupled plasma atomic emission spectroscopy. Gd3+ blood concentration/time data were analyzed nonparametrically and parametrically using the software program WinNonlin VI.1. RESULTS:Mean (SD) values for Gd3+ area under the curve, blood clearance, steady-state volume of distribution, renal clearance, andcreatinine clearance for the moderate group were 862 (392) micrograms.h/mL, 56 (25) mL/min, 21 (5) L, 47 (23) mL/min, and 46 (16) mL/min. Values for the severe group were 1347 (366) micrograms.h/mL, 31 (7) mL/min, 19 (6) L, 22 (7) mL/min, and 21 (8) mL/min. No Gd(3+)-relatedadverse events occurred. Mean values for Gd3+ recovery in urine and feces for moderate and severe groups were 74% and 6%, and 69% and 8% of the dose, respectively. Linear regression analysis demonstrated a significant relation between the level of renal function and blood clearance of Gd3+. CONCLUSIONS: Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.
RCT Entities:
RATIONALE AND OBJECTIVES: To determine the safety and pharmacokinetics of gadobenate dimeglumine in a group of subjects with moderate or severe renal impairment. METHODS: The safety and pharmacokinetic profile of gadobenate dimeglumine, a gadolinium (Gd3+) chelate complex in development as a contrast agent for MRI, were evaluated in a placebo-controlled, double-blind, multicenter trial. Subjects with moderate or severe renal impairment (creatinine clearances of 31 to 60 or 10 to 30 mL/min, respectively) received a 0.2-mmol/kg intravenous bolus of Gd3+ or saline placebo. Blood samples (up to 72 hours) and urine and fecal samples (up to 216 hours) were assayed for total Gd3+ content by inductively coupled plasma atomic emission spectroscopy. Gd3+ blood concentration/time data were analyzed nonparametrically and parametrically using the software program WinNonlin VI.1. RESULTS: Mean (SD) values for Gd3+ area under the curve, blood clearance, steady-state volume of distribution, renal clearance, and creatinine clearance for the moderate group were 862 (392) micrograms.h/mL, 56 (25) mL/min, 21 (5) L, 47 (23) mL/min, and 46 (16) mL/min. Values for the severe group were 1347 (366) micrograms.h/mL, 31 (7) mL/min, 19 (6) L, 22 (7) mL/min, and 21 (8) mL/min. No Gd(3+)-related adverse events occurred. Mean values for Gd3+ recovery in urine and feces for moderate and severe groups were 74% and 6%, and 69% and 8% of the dose, respectively. Linear regression analysis demonstrated a significant relation between the level of renal function and blood clearance of Gd3+. CONCLUSIONS: Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.
Authors: Eric M Gale; Peter Caravan; Anil G Rao; Robert J McDonald; Matthew Winfeld; Robert J Fleck; Michael S Gee Journal: Pediatr Radiol Date: 2017-04-13