Pharmacokinetic Characterization of Iopamidol and Iohexol for Optimizing Measured Glomerular Filtration Rate...

Accurate kidney function assessment supports healthcare and clinical decision-making in practice and drug development. Measured glomerular filtration rate (mGFR) via iohexol clearance is the gold standard, but cost, supply issues, and logistical challenges limit its clinical use. Iopamidol, another iodinated contrast agent widely used in CT imaging, has not been studied in humans for mGFR assessment. This study aims to evaluate the pharmacokinetic interchangeability of iohexol and iopamidol for mGFR assessment and to develop a limited sampling strategy to facilitate clinical implementation. In a parallel-group, single-dose pharmacokinetic study, 24 healthy adult volunteers with varying kidney function, as defined by the 2021 CKD-EPI eGFRcr equation (range: 35-140 mL/min; median: 72 mL/min), received iohexol and iopamidol. Plasma concentrations were measured using liquid chromatography-mass spectrometry, and population pharmacokinetic modeling estimated drug clearance. Clearance estimates for both agents showed strong agreement (R² = 0.82, P < .005), with Bland-Altman analysis indicating minimal bias (mean difference: 15.69 mL/min; LoA: -3.76 to 35.15). A limited sampling strategy using one (1-h, R² = 0.91) or two (1 and 5 h, R² = 0.92) time points yielded accurate clearance estimates. These findings suggest that iopamidol may be a viable alternative to iohexol for mGFR determination. Broader access to accurate kidney function testing can enhance drug dosing, reduce misclassification, and improve care for patients with chronic kidney disease. Further research should validate these findings in larger, more diverse populations, including those with advanced kidney impairment.