Clinical Pharmacokinetics of Gentamicin

Objectives: The objectives of this study were to: (1) derive equations for estimating gentamicin clearance (Cl gent ) and volume of distribution (V d ) based on the local population attendingAl-Amiri Hospital, Kuwait; (2) independently evaluate these equations by comparison with other published methods in their predictive ability to estimate Cl gent and V d . Materials and Methods: Cl gent and V d were calculated in 47 patients (group 1) using the Sawchuk-Zaske method. Regressionanalysis was used to derive a correlation between creatinine clearance (Cl cr ) and Cl gent , V d and actual body weight (ABW). Based on actual Cl gent and V d values, the predictive ability of the estimated parameters from the regression equations was validated and compared with 4 publishedmethods 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. Results: The mean 8 SD values of Cl gent and V d were 4.0 8 1.8 l h –1 and 16.8 8 6.7liters, respectively. The derived equations were: Cl gent = (0.760) (Cl cr ) + 1.117 (r = 0.701) and V d = (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 Cl gent (p !0.05), and less biased (ME = –0.01) with no difference in precision (MSE = 36.22, RMSE = 4.59) in predicting V d (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 Cl gent (p 0.05), whilst no difference was found for prediction of V d (p 0.05). Conclusion: The equations developed in this study provided a reliable estimation of Cl gent and V d . It is planned to use them at Kuwait Hospitals to help provide more individualized patient dosing information tophysicians.