Comparison of the Cockcroft–Gault, MDRD and CKD‐EPI equations for estimating ganciclovir clearance

• Published in: British journal of clinical pharmacology Vol. 84; no. 9; pp. 2120 - 2128
• Main Authors: Palacio‐Lacambra, Maria‐Eugenia, Comas‐Reixach, Immaculada, Blanco‐Grau, Albert, Suñé‐Negre, Josep‐Maria, Segarra‐Medrano, Alfonso, Montoro‐Ronsano, José‐Bruno
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.09.2018
• Subjects: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Area Under Curve; CKD‐EPI equation; clearance; Cockcroft–Gault equation; Cytomegalovirus Infections - drug therapy; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; ganciclovir; Ganciclovir - administration & dosage; Ganciclovir - pharmacokinetics; Glomerular Filtration Rate - physiology; Humans; Male; MDRD study equation; Metabolic Clearance Rate - physiology; Middle Aged; Models, Biological; Original; renal dosage adjustments; Renal Elimination - physiology; Renal Insufficiency, Chronic - physiopathology; Retrospective Studies; Young Adult; MDRD study equation; renal dosage adjustments; clearance; ganciclovir; CKD-EPI equation; Cockcroft-Gault equation
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.13647

Aims Accurately estimating kidney function is essential for the safe administration of renally cleared drugs such as ganciclovir. Current practice recommends adjusting renally eliminated drugs according to the Cockcroft–Gault equation. There are no data on the utility of the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equations in ganciclovir dosing. To evaluate which renal function equation best predicts ganciclovir clearance. Methods The performance of the Cockcroft–Gault equation, isotope dilution mass spectrometry (IDMS)‐traceable 4‐variable MDRD study (MDRD4‐IDMS) equation and CKD‐EPI equation in determining ganciclovir clearance were assessed retrospectively in patients treated with ganciclovir from 2004–2015. The MDRD4‐IDMS and CKD‐EPI equations adjusted to individual body surface area (MDRD4‐IDMS·BSA and CKD‐EPI·BSA, respectively) were also evaluated. Patients with intravenous ganciclovir peak and trough concentrations in their medical records were included in the study. Ganciclovir clearance was calculated from serum concentrations using a one‐compartment model. The five equations were compared based on their predictive ability, the coefficient of determination, through a linear regression analysis. The results were validated in a group of patients. Results One hundred patients were included in the final analysis. Seventy‐four patients were analysed in the learning group and 26 in the validation group. The coefficient of determination was 0.281 for Cockcroft–Gault, 0.301 for CKD‐EPI·BSA, 0.308 for MDRD4‐IDMS·BSA, 0.324 for MDRD4‐IDMS and 0.360 for CKD‐EPI. Subgroup analysis also showed that CKD‐EPI is a better predictor of ganciclovir clearance. Analysis of the validation group confirmed these results. Conclusions The CKD‐EPI equation correlates better with ganciclovir clearance than the Cockcroft‐Gault and MDRD4‐IDMS equations, even the clinical difference between the equations is scarce.