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 attending Al-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. Regression analysis 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 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. Results: The mean ± SD values of Cl _gent and V_d were 4.0 ± 1.8 l·h^-1 and 16.8 ± 6.7 liters, 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 to physicians.