ISSN: 2578-4803
Effect of Kidney Function on Amikacin Pharmacokinetics on Hospitalized Patients: Knowledge to Improve Therapy
Authors:
Gonçalves C1, Rocha M2, Gonçalves J1,3, Falcão A1,3, and Ana Fortuna1,3*
Despite the narrow therapeutic window characteristic of amikacin, this amino glycoside remains one of the most frequently prescribed particularly against multiple drug-resistant pathogens. In order to achieve an effective antibiotic therapeutic effect with minimal toxicity and, simultaneously avoid bacterial resistance development, the pharmacokinetics drug monitoring is recommended for amikacin. Since amikacin is almost 100% eliminated by glomerular filtration and it is nephro- and ototoxic, its exposure and availability in renal patients is expected to be altered in relation to patients with normal organ function. In this context, the present study aimed at assessing the correlation between demographical/biochemical data and the pharmacokinetic parameters of amikacin in an attempt of developing dosage recommendations to renal patients. The present retrospective study included 628 patients undergoing therapy with amikacin and admitted in Coimbra University Hospital pole of the Hospital and University Centre of Coimbra, EPE, in Portugal, between 2008 and 2015. Blood samples were collected 1 h after the end of amikacin infusion and 30 min before the following administration to attain the peak concentration (Cmax) and the trough concentration (Cmin). Demographic data, dose and frequency of administration of amikacin and creatinemia were also collected for each patient, whose pharmacokinetic parameters were then calculated using equations Sawchuk and Zaske. The population was divided regarding the age of each patient (18-34; 35-49; 50-64; 65-79 and ≥80 years old) and regarding the glomerular filtration rate: <60, 60-120 and ≥120 mL/min/1.73m2.
After checking the normality and homogeneity of variances test, ANOVA was used to determine statistical differences among those distinct sub-populations. Statistically significant differences were found between the 5 age groups regarding half-life time (t1/2), elimination constant (ke), and clearance of amikacin, but not for the apparent volume of distribution (VD): diminished values of clearance and ke were found as the age enhanced, while the t1/2 increased. Furthermore mean values of Cmax maintained constant while those of Cmin increased from 1.82 μg/mL, in the youngest group, to 6.44 μg/mL in the oldest group. Regarding renal function, as the CLcr enhanced, the clearance and ke of amikacin increased, contributing to lower values of Cmin (mean values of 7.15 μg/mL versus 3.14 μg/mL).
At the end, it was herein demonstrated, that as age increases and/or renal function decreases, the clearance of amikacin diminished and its t1/2 augmented, although no differences were found on the volume of distribution of amikacin. This suggests that in elderly and renal patients, amikacin doses should be lower than those administered to young adults with no commitment of renal activity. Nevertheless, administration interval may have to be prolonged to guarantee no toxic accumulation of amikacin.
Keywords:
Amikacin; Amino glycosides; Renal disease; Pharmacokinetic drug monitoring; Bacterial resistance
