Performance of two predictive methods for calculation of the key pharmacokinetic parameters for gentamicin dosage individualization.

Performance of two methods for determination of the apparent volume of distribution (Vd) and the elimination half-life (t1/2) for gentamicin was evaluated in 20 non-obese acutely ill patients. The patients had varying degrees of renal function. Initial creatinine clearance ranged from 22.7-103.1 ml/min, with a mean value (+/- SEM) of 63.26 (+/- 5.74) ml/min, and serum creatinine concentration was 1.37 (+/- 0.13) mg/dl, with a range of 0.70-3.0 mg/dl. The total daily dose of gentamicin ranged from 1.85-4.71 mg/kg. Two different methods were used for Vd calculation: the Hull-Sarubbi method and Chiou midpoint-back-extrapolation method. For t1/2 estimation, the Hull-Sarubbi and Cutler methods were used. These values were compared with the values obtained by the Sawchuk-Zaske method. Mean predicted error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were calculated for each method. Prediction bias and precision were compared statistically between each method by calculating the 95% confidence intervals of the delta MA and delta MAE, respectively. The MAEs revealed that the precision of Vd predictions were within 1.04 litre and 0.62 litre for the Hull-Sarubbi and Chiou methods, respectively. For the elimination half-life, none of the methods performance exhibited substantial bias. The Hull-Sarubbi method, however, was less biased and more precise than the Cutler method.