Clinical pharmacokinetics of gentamicin. Estimation of initial dosing parameters in hospitalized patients at Al-Amiri Hospital Kuwait

The objectives of this study were to: [1] derive equations for estimating gentamicin clearance [Clgent] and volume of distribution [Vd] based on the local population attending Al-Amiri Hospital, Kuwait; [2] independently evaluate these equations by comparison with other published methods in their predictive ability to estimate Clgent and Vd. Clgent and Vd were calculated in 47 patients [group 1] using the Sawchuk-Zaske method. Regression analysis was used to derive a correlation between creatinine clearance [Clcr] and Clgent, Vd and actual body weight [ABW]. Based on actual Clgent and Vd values, the predictive ability of the estimated parameters from the regression equations was validated and compared with 4 published methods using mean error [ME], i.e. bias, and mean squared error [MSE] and root mean squared error [RMSE], i.e. precision. All equations were also evaluated in an independent second group [group 2] of 23 patients. The mean +/- SD values of Clgent and Vd were 4.0 +/- 1.8 lúh-1 and 16.8 +/- 6.7 liters, respectively. The derived equations were: Clgent = [0.760] [Clcr] + 1.117 [r = 0.701] and Vd = [0.165] [ABW] + 5.604 [r = 0.532]. In comparison to the 4 published methods, the derived equations were less biased [ME = 0.00] and more precise [MSE = 1.68, RMSE = 1.02] in predicting Clgent [p < 0.05], and less biased [ME = -0.01] with no difference in precision [MSE = 36.22, RMSE = 4.59] in predicting Vd [p > 0.05]. This precision was confirmed in the second group of 23 patients, where the derived equations were less biased [ME = -0.1] and more precise [MSE = 3.22, RMSE = 1.48] in predicting Clgent [p < 0.05], whilst no difference was found for prediction of Vd [p > 0.05]. The equations developed in this study provided a reliable estimation of Clgent and Vd. It is planned to use them at Kuwait Hospitals to help provide more individualized patient dosing information to physicians

Therapeutic drug monitoring of gentamicin: evaluation of five nomograms for initial dosing at Al-Amiri Hospital in Kuwait

To compare five published nomograms [Thomson guidelines, Mawer nomogram, rule of eights, Hull-Sarubbi table and Dettli method] for calculating the initial gentamicin dosage regimen in a Kuwaiti population. Based on measured peak and trough gentamicin concentrations, the elimination rate constant and volume of distribution of gentamicin were calculated for each patient [n = 56], using a modified two-point Sawchuk-Zaske method. The calculated individual set of pharmacokinetic parameters and the initial dose regimen recommended by each of the five methods were used to predict the steady-state peak and trough of gentamicin concentrations. The Thomson guidelines produced consistent results in predicting gentamicin concentrations within the target ranges of peak plus trough, peak only and trough only [63, 75 and 75%, respectively]. The Mawer nomogram, Hull-Sa-rubbi table and Dettli methods achieved similar percentages of patients [46-50%] within the target ranges [5-10 mg l[-1] for peak and 0.5-2 for trough], whereas empirical dosing and the rule of eights showed the lowest percentages of patients within the peak plus trough target range [25 and 37%, respectively]. However, with respect to the underdosing target range [predicted concentration <5 mg l[-1]], the Thomson guidelines showed that 21% of patients were underdosed. The results show that a large number of patients [37-63%] were outside the target ranges in all initial gentamicin dosing methods evaluated in this study. Therefore, serum concentration measurement can be advised to assist in the optimization of gentamicin dose selection