A Model of Dosing Agreement Among Various Methods of Estimating Creatinine Clearance

Eptifibatide is a glycoprotein IIb/IIIainhibitor used to inhibit platelet ag-gregation and prevent thromboses in pa-tients with acute coronary syndrome. Re-nal clearance of eptifibatide accounts for approximately 50 % of total body clear-ance, with the majority of the drug excret-ed in the urine unchanged or as metabo-lites.1 In patients with moderate-to-severe renal insufficiency, the clearance of the drug is decreased by approximately half. To prevent dangerous drug accumulation, the manufacturer of eptifibatide recom-mends that after the initial bolus, the con-tinuous infusion dose should be adjusted from 2 µg/kg/min to 1 µg/kg/min for all patients with moderate-to-severe renal in-sufficiency. Based on pharmacokinetic studies, this is further defined as a creati-nine clearance (CrCl) less than 50 mL/min as calculated by the Cockcroft-Gault (CG) formula using actual body weight (ABW).1,2 Medications that are renally eliminat-ed often require dosing adjustments to protect patients from harmful drug accu-mulation. While the most precise mecha-nism in determining renal function is di-rect measurement of glomerular filtration rate (GFR) using an exogenous marker, this is costly and unfeasible in clinical practice. A common alternative is to use the clearance of an endogenous marker, creatinine, as an es-timate of renal function. CrCl can be determined using 24-hour urine creatinine measurements but is more commonly estimated from serum creatinine (SCr) levels manipulated with an equation that takes several relevant patient parame-ters into consideration. The most prominent example is the CG equation, which was developed in 1973 to mathemati