Pharmacokinetics of 1M gadobutrol in patients with chronic renal failure

RATIONALE AND OBJECTIVES. TO investigate the pharmacokinetics of 1M gadobut rol as a new neutral MR contrast agent in patients with impaired renal func tion. METHODS. Twenty-one patients with impaired renal function and any indicatio n for a contrast-enhanced MRI were enrolled into this prospective study and classified in two subgroups according to their creatinine clearance (group 1, 30-80 mL/ min; group 2, 30 mL/min or less, not requiring dialysis), Ele ven patients were assigned to the lower dose of 0.1 mmol Gd/kg and 10 patie nts to the higher dose of 0.3 mmol Gd/kg, To calculate pharmacokinetic para meters, urine and venous blood samples were drawn at baseline and up to 72 hours for group 1 and 120 hours for group 2 after administration of gadobut rol, RESULTS. The predominant extracellular distribution of gadobutrol at steady state did not change according to the degree of renal impairment. The mean elimination half-life of gadobutrol increased to 7.4 +/- 2.6 hours (0.1 mm ol/kg) and 5.4 +/- 1.5 hour (0.3 mmol/kg) in group 1 and to 17.9 +/- 6.2 ho urs (0.1 mmol/kg) and 20.4 +/- 16.9 hours (0.3 mmol/kg) in group 2, compare d with 1.5 hours in healthy volunteers. The relation between serum (t(beta) ) and urine (t(elim)) elimination half-lives, as well as total serum and re nal clearance, indicated renal elimination as the main pathway of eliminati on. The recovery of gadobutrol in the urine of group 1 was complete within 72 hours for both dosage levels. Patients with severe renal impairment show ed a mean recovery of 80.1% (0.1 mmol/kg) and 85.3% (0.3 mmol/kg) within th e observation period of 120 hours. CONCLUSIONS. The half-life of gadobutrol is prolonged in patients with impa ired renal function, but elimination by means of the kidneys is the predomi nant route.