However, there is evidence that iohexol pharmacokinetics is best described by a three-compartment model 4, suggesting that estimates obtained by the Schwartz approach are subject to avoidable bias. This approach assumes a double-exponential decay of iohexol plasma concentrations and thus represents a two-compartment model. Recently published GFR prediction equations, such as the Berlin Initiative Study (BIS) 2, rely on iohexol clearance estimates obtained via the Schwartz approach 3.

Three-compartment models should be employed to assess iohexol pharmacokinetics.īecause of its favorable pharmacokinetic properties and better availability compared to inulin, plasma clearance of iohexol has become a key tool to determine glomerular filtration rate (GFR) 1 accurately. Predictions based on the BIS2 equation were biased (5.4 mL/min/1.73 m²) and the sensitivity to detect a GFR < 60 mL/min/1.73 m² was low compared to the revised equation (72% versus 89%). Compared to the three-compartment model, clearance values were overestimated by the Schwartz approach (bias 6.5 mL/min), resulting in limited effects on regression coefficients of the BIS equations (e.g., proportionality factor of BIS2 changed from 767 to 720). A three-compartment model appropriately described the pharmacokinetics of iohexol (clearance 57.4 mL/min, CV 33%). A popPK model was developed based on iohexol plasma samples (8–10 per subject, iohexol dose 3235 mg) from 570 elderly patients. We aimed to provide a population pharmacokinetic (popPK) model of iohexol by re-evaluating data from the Berlin Initiative Study (BIS) to compare respective clearance estimates to the Schwartz approach and to assess the impact of revised clearance estimates on the BIS equations. Despite evidence that iohexol pharmacokinetics are described best by three-compartment models, two-compartment approaches (Schwartz approach) are customary, which might result in avoidable bias and imprecision. Plasma clearance of iohexol is a key tool to precisely determine glomerular filtration rate (GFR) in clinical research and clinical practice.

Nonmem 3 compartment