Validating Low-Dose Iohexol as a Marker for Glomerular Filtration Rate by In Vitro and In Vivo Studies.

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Nephrology and Renal Physiology

Background:

• Intravenous iohexol administration is standard for assessing glomerular filtration rate (GFR).
• Systematic evaluation of iohexol's pharmacokinetic (PK) properties and potential drug transporter interactions is incomplete.

Purpose of the Study:

• To investigate potential interactions between iohexol and key drug transporters.
• To determine if a lower dose of iohexol (259 mg) can effectively replace the standard dose (3235 mg) for GFR assessment.

Main Methods:

• In vitro studies assessed iohexol's interaction with renal and other drug transporters using cell-based and vesicle-based systems.
• A clinical trial in 12 volunteers compared PK properties of 3235 mg (reference) and 259 mg (test) intravenous iohexol doses.
• Population PK analysis characterized iohexol's elimination profile.

Main Results:

• In vitro, iohexol was neither a substrate nor a significant inhibitor of tested drug transporters.
• Clinical trial demonstrated dose linearity; the test/reference ratio for plasma clearance was 1.01 (90% CI: 0.968–1.05).
• Population PK analysis confirmed dose-independent renal clearance and negligible nonrenal clearance.

Conclusions:

• Iohexol is unlikely to be involved in transporter-mediated drug-drug interactions.
• A lower dose of iohexol (259 mg) is suitable for precise GFR measurement.
• Low-dose iohexol serves as a reliable GFR marker, even with co-administered medications.