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

RATIONALE AND OBJECTIVES. TO present the results of two studies conducted t o evaluate the pharmacokinetics and safety of iomeprol in healthy volunteer s and in patients,vith various degrees of renal impairment. METHODS. In these two open-label, single-dose, phase I studies, a 50-mL dos e of iomeprol 400 was administered intravenously to a total of 30 subjects of either sex. In study 1, six healthy volunteers with normal renal functio n, six patients with mild renal failure, six patients with moderate renal f ailure, 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) me asurement of vital signs, hematology, blood chemistry, urinalysis, electroc ardiogram, physical examinations, and the incidence of adverse events. Phar macokinetics 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 b oth healthy subjects and patients. As expected, mean body and renal clearan ces decreased progressively with increasing renal impairment, with a signif icant correlation with the glomerular filtration rate. The elimination half -life increased progressively,vith increasing renal impairment. The extract ion 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/mi n), slightly less than the body clearance previously observed in healthy su bjects. It appears that dialysis is almost as efficient as renal function i n healthy subjects in the removal of iomeprol. After a single dialysis sess ion, approximately 58% of the dose was recovered in dialysate. Mild to mode rate 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 wit h renal impairment and in patients receiving dialysis. No dose adjustment a ppears to be necessary either in patients with renal impairment or with end -stage renal disease requiring hemodialysis. In this risk population, iomep rol 400 was safe and well tolerated.