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


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 x 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).


CONCLUSIONS
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.
Department of Pharmacy, Al-Amiri Hospital, Ministry of Health, Kuwait University, Kuwait. yousefl@hsc.edu.kw
Yousef
Y
Al-Lanqawi
Philip
P
Capps
Kefaya
K
Abudlmalek
Khalid
K
Al-Anezi
Anail
A
Thusu
Prem
P
Sharma
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015982:Bias; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006761:Hospitals; D006801:Humans; D007730:Kuwait; D008297:Male; D015233:Models, Statistical; D012044:Regression Analysis
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003404:Creatinine