Population pharmacokinetics of netilmicin in short-term prophylactic treatment

To characterize the population pharmacokinetics of netilmicin, an aminoglycoside antibiotic, in adult urology patients and to develop a covariate model for improved dose titration.

Data from 62 adult patients (55 male, seven female), undergoing urological surgery and treated with netilmicin for short-term prophylaxis, were evaluated retrospectively. The group had (median, range) ages 68, 31-92 years, weights 72, 43-106 kg and heights 167, 148-182 cm. No patient showed renal impairment before netilmicin treatment (serum creatinine

A bi-compartmental open model with a proportional residual error best described the data. The population parameters for central and peripheral volumes of distribution were (typical population value [interindividual CV%]) Vc = 14.5 l [56%] and Vp = 10.2 l [not estimated], and the systemic and intercompartmental clearances were CL = 3.9 l h-1[42%] and CLQ = 10.1 l h-1[not estimated], respectively. The final population covariate relationships were based on sex (SEX) and creatinine clearance (CrCL): (Vc, l) = 18.9 - 5.9 x SEX [29%] and (CL, l h-1) = 0.06 x CrCL [33%]. Compared with the observations in the validation group, this model showed a bias (95% confidence interval) of -0.028 (-0.28, 0.25) and precision of 1.22 (0.78, 1.34).

Bi-compartmental pharmacokinetic parameters of netilmicin have been estimated from clinical data in urological surgery patients using a population approach. A given single dose results in large variability in plasma concentrations and thus the population covariate final model can be used for direct estimation of initial dosing in patients.