Pharmacokinetics and safety of iomeprol in healthy volunteers and in patients with renal impairment or end-stage renal disease requiring hemodialysis.

摘要

RATIONALE AND OBJECTIVES: To present the results of two studies conducted to evaluate the pharmacokinetics and safety of iomeprol in healthy volunteers and in patients with various degrees of renal impairment. METHODS: In these two open-label, single-dose, phase I studies, a 50-mL dose of iomeprol 400 was administered intravenously to a total of 30 subjects of either sex. In study 1, six healthy volunteers with normal renal function, six patients with mild renal failure, six patients with moderate renal failure, and four patients with severe renal failure were enrolled. In study 2, eight patients with end-stage renal disease requiring hemodialysis were enrolled. Safety was determined by predose and postdose (up to 10 days) measurement of vital signs, hematology, blood chemistry, urinalysis, electrocardiogram, physical examinations, and the incidence of adverse events. Pharmacokinetics was determined by measuring iomeprol levels in plasma, urine, feces, and dialysate samples, by using a validated high-performance liquid chromatography assay, up to 7 days after administration. RESULTS: The plasma concentration of iomeprol declined biexponentially in both healthy subjects and patients. As expected, mean body and renal clearances decreased progressively with increasing renal impairment, with a significant correlation with the glomerular filtration rate. The elimination half-life increased progressively with increasing renal impairment. The extraction efficiency of dialyser was estimated as approximately 40%, and dialysis clearance of iomeprol was approximately 1.26 mL. min-1. kg-1 (80.6 mL/min), slightly less than the body clearance previously observed in healthy subjects. It appears that dialysis is almost as efficient as renal function in healthy subjects in the removal of iomeprol. After a single dialysis session, approximately 58% of the dose was recovered in dialysate. Mild to moderate adverse events were reported by 17 of 30 subjects; none was clinically meaningful. One serious adverse event, unrelated to iomeprol, was reported. No clinically meaningful findings were noted for other safety parameters. CONCLUSIONS: Iomeprol was almost completely eliminated both in patients with renal impairment and in patients receiving dialysis. No dose adjustment appears to be necessary either in patients with renal impairment or with end-stage renal disease requiring hemodialysis. In this risk population, iomeprol 400 was safe and well tolerated.