Modification of Diet in Renal Disease and modified Cockcroft-Gault formulas in predicting aminoglycoside elimination.
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.
Bookstaver
P Brandon
PB
College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA. bookstaver@sccp.sc.edu
Johnson
James W
JW
McCoy
Thomas P
TP
Stewart
David
D
Williamson
John C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001830:Body Surface Area; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D005260:Female; D005544:Forecasting; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D000583:Amikacin; D014031:Tobramycin