Pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily

Abstract

Aims 1. To determine the population pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily. 2. To see if current starting doses for once daily aminoglycoside dosing are appropriate. 3. To test whether calculating creatinine clearance using an adjusted Cockcroft and Gault method (CL Cr,adjusted ) was a better predictor of gentamicin clearance than the standard Cockcroft and Gault method (CL Cr,unadjusted =0.80) was a better predictor of gentamicin CL than CL Cr,unadjusted (r 2 =0.57). Conclusions The mean population values of V d and CL of gentamicin dosed once daily are similar to those described by others in relation to multiple daily dosing. Given that previous methods have been based on population values of V d and CL from multiple daily dosing, the currently recommended starting doses for once daily aminoglycoside dosing would seem appropriate. The V d reduced with decreasing renal function, with a maximum of 23% difference between patients with normal and poor renal function. The Cockcroft and Gault method of calculating creatinine clearance does not appear to perform well at low values of serum creatinine concentration. An adjustment of the Cockcroft and Gault method is proposed to allow for this.

Rounding of low serum creatinine levels and consequent impact on accuracy of bedside estimates of renal function in cancer patients

“…These results are supported by a pharmacokinetic study performed in patients with varying renal function who were treated with gentamicin daily (Kirkpatrick et al, 1999). The clearance of gentamicin was more accurately predicted when low levels of Scr were also capped at 0.06 mmol l À1 .…”

Flat Dosing of Carboplatin Is Justified in Adult Patients with Normal Renal Function

“…4A-C) seen in our population. In the work of Kirkpatrick et al (29), S CR values <60 Amol/L were set at 60 Amol/L in patients receiving gentamicin because it was thought that low values of S CR may reflect decreased production rather than enhanced clearance. In our population, S CR values were <60 Amol/L in more than half the patients probably due to the disease condition of these patients.…”

The performances of the Cockcroft-Gault, Modification of Diet in Renal Disease Study and Chronic Kidney Disease Epidemiology Collaboration equations in predicting gentamicin clearance

“…The utility of setting the minimum serum creatinine concentrations at 60 mmol/L has previously been demonstrated for the Cockcroft-Gault equation in the setting of IBW as the weight descriptor in relation to gentamicin clearance. 19 This has also been demonstrated for carboplatin, 44 and reflects the idea that low serum creatinine concentrations may be a consequence of low muscle mass and thus low creatinine production, rather than high creatinine clearance. However, in the current study there was little change in the bias and imprecision when a minimum creatinine of 60 mmol/L was applied to either the Cockcroft-Gault or MDRD Study equations.…”

“…Third, while it is intuitive that correcting the results from the MDRD Study and CKD-EPI equations for individual BSAs should improve the prediction of renal drug clearance in individuals, this has not been demonstrated in previous research. 18 Finally, while setting the serum creatinine concentration at a minimum of 60 mmol/L has been shown to improve the performance of the Cockcroft-Gault equation, 19 this has not been systematically examined either in the context of various weight descriptors being used in the Cockcroft-Gault equation or in the MDRD Study equation.…”