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CLINICAL PHARMACOKINETICS

Modification of Diet in Renal Disease and Modified Cockcroft-Gault Formulas in Predicting Aminoglycoside Elimination

Clinical Assistant Professor, College of Pharmacy, University of South Carolina, Columbia, SC

James W Johnson, PharmD BCPS

Clinical Coordinator, Infectious Diseases, Department of Pharmacy, Wake Forest University, Baptist Medical Center, Winston-Salem, NC

Thomas P McCoy, MS

Biostatistician, Department of Biostatistical Sciences, Wake Forest University Health Sciences

David Stewart, PharmD BCPS

Clinical Assistant Professor, College of Pharmacy, East Tennessee State University, Johnson City, TN

John C Williamson, PharmD BCPS

Clinical Coordinator, Infectious Diseases, Department of Pharmacy, Wake Forest University, Baptist Medical Center

Reprints: Dr. Bookstaver, College of Pharmacy, University of South Carolina Campus, 715 Sumter St., Columbia, SC 29208, fax 803/777-1943, bookstaver{at}sccp.sc.edu

BACKGROUND: The Modification of Diet in Renal Disease (MDRD) formula and a modified version of the Cockcroft-Gault (CG_m) formula adjusting for body surface area have been found to more accurately estimate glomerular filtration rate (GFR) compared with the original CG equation in specific patient populations. To date, the use of these formulas in determining drug dosage and estimating drug elimination has not been thoroughly investigated.

OBJECTIVE: To evaluate the ability of the MDRD and CG_m formulas to predict aminoglycoside elimination rate and clearance.

METHODS: A 6-month prospective, noninterventional, pharmacokinetic study was conducted at a university teaching hospital. Patients receiving aminoglycoside antibiotics (amikacin, gentamicin, or tobramycin) were eligible for study inclusion. Predicted elimination rate and aminoglycoside clearance were calculated for each patient using the MDRD and CG_m formulas. Actual (patient-specific) elimination rate and aminoglycoside clearance were calculated for each patient using measured aminoglycoside serum concentrations. Predictive ability of the formulas was compared through Spearman correlations and Student's t-tests. Accuracy of formula estimates was also evaluated.

RESULTS: Seventy-one patients met study inclusion criteria; the majority (82%) were in an intensive care unit. The 6-variable MDRD formula was found to be a significantly better predictor of aminoglycoside clearance (p = 0.035) compared with CG_m. There was no statistically significant difference between the 2 methods in predicting patient-specific elimination rates (p = 0.167). Among subgroups, the MDRD formula was a significantly better predictor of aminoglycoside clearance for patients with an estimated GFR less than 60 mL/min (p = 0.027).

CONCLUSIONS: The 6-variable MDRD performs better than the CG_m formula in predicting aminoglycoside clearance and may be considered as a tool in aminoglycoside dosing recommendations.

Key Words: aminoglycoside dosing, Cockcroft-Gault, Modification of Diet in Renal Disease, modified Cockcroft-Gault, renal drug dosing

Published Online, November 25, 2008. www.theannals.com, DOI 10.1345/aph.1L144

This article has been cited by other articles:

				S. Goutelle, L. Bourguignon, M. Ducher, and P. Maire Comment: Modification of Diet in Renal Disease and Modified Cockcroft-Gault Formulas in Predicting Aminoglycoside Elimination Ann. Pharmacother., June 1, 2009; 43(6): 1145 - 1146. [Full Text] [PDF]