Contrast dose-to-creatinine clearance ratio as a potential indicator of risk for radiocontrast-induced nephropathy: correlation of D/CrCL with area under the contrast concentration-time curve using iodixanol.

OBJECTIVES: Identification of risk factors is important for preventing radiocontrast-induced nephropathy (RCIN). Contrast dose and renal function have been shown in most but not all studies to be risk factors for RCIN. We are investigating the ratio of contrast dose to creatinine clearance (D/CrCL) as a risk indicator. Theory shows that the D/CrCL ratio equals the area under the concentration-time curve (AUC), an accepted measure of systemic exposure. This study investigated the correlation between calculated D/CrCL and experimentally measured AUC for the contrast agent iodixanol. MATERIALS AND METHODS: Experimental data on AUC from a phase 1 study of iodixanol were plotted against the D/CrCL ratio and the degree of correlation was determined. RESULTS: Experimentally determined AUC data correlate highly with the D/CrCL ratio. CONCLUSIONS: The D/CrCL ratio is a rapid and accurate way to estimate AUC for an iodinated x-ray contrast agent without the need for multiple blood samples.

The OptiMARK clinical development program: summary of safety data.

PURPOSE: To describe and summarize the safety data from the OptiMARK clinical development program. MATERIALS AND METHODS: In the 18 clinical studies comprising the clinical program, doses ranging from 0.1 to 0.7 mmol/kg were administered to healthy adult volunteers, patients with hepatic or renal impairment, and patients with confirmed or highly suspected central nervous system (CNS), liver, breast, vascular, bone, or soft tissue pathologies. A total of 2038 injections of OptiMARK, Magnevist, or placebo were administered to 1684 subjects. Safety assessments were performed at appropriate intervals during all Phase 1, 2, and 3 studies. RESULTS: Of the 1684 subjects exposed to a study drug or placebo in the clinical development program, 646 subjects experienced 1293 adverse events. Thirty-one percent of the OptiMARK injections were associated with an adverse event. In comparison, 35% of Magnevist injections and 48% of placebo injections were associated with at least one adverse event. CONCLUSIONS: OptiMARK was safe and well-tolerated with a safety profile similar to that of Magnevist.