Population Pharmacokinetics of Amikacin Administered Once Daily in Patients with Different Renal Functions

Abstract

The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the influence of clinical and demographical covariates that may influence the optimization of this antibiotic. A prospective study was performed in a total of 63 patients with at least one determination of amikacin plasma concentration. Population pharmacokinetic (PK) parameters were estimated by nonlinear mixed-effects modeling; validations were performed for dosing recommendation purposes based on PK/pharmacodynamic simulations. The concentration-versus-time data were best described by a one-compartment open model with proportional interindividual variability associated with amikacin clearance (CL) and volume of distribution (V); residual error followed a homoscedastic trend. Creatinine clearance (CLCR) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and V, respectively. The final model [CL (liters/h) = 7.1 × (CLCR/130)0.84 and V (liters) = 20.3 × (IBW/68)2.9] showed a mean prediction error of 0.11 mg/liter (95% confidence interval, −3.34, 3.55) in the validation performed in a different group of patients with similar characteristics. There is a wide variability in amikacin PK parameters in Mexican patients. This leads to inadequate dosing regimens, especially in patients with augmented renal clearance (CLCR of >130 ml/min). Optimization based on the final population PK model in Mexican patients may be useful, since reliability and clinical applicability have been demonstrated in this study.

Synthesis, biological activities and docking studies of pleuromutilin derivatives with piperazinyl urea linkage

“…Natural products such as Penicillin, Erythromycin, Cephalosporin C and Kanamycin are often used as main compounds in drug discoveries due to their potent bioactivity. Corresponding semi-synthesised derivatives Amoxicillin, Azithromycin, Cefpirome and Amikacin all exhibit higher potency than natural products [5][6][7] . Pleuromutilin (Figure 1, 1), a diterpenoid natural product from the basidiomycete species, shows moderate activities against Gram-positive strains and mycoplasmas 8,9 .…”

Augmented Renal Clearance and How to Augment Antibiotic Dosing

“…Aminoglycosides are concentration-dependent agents and require a C max /MIC of 10 [ 61 ]. Two population pharmacokinetic studies focusing on amikacin concluded that ARC patients likely require increased dosing regimens [ 62 , 63 ]. Another pharmacokinetic modeling study in pediatric ICU patients who were administered tobramycin or gentamicin observed significantly lower median 24-h AUC (45.27 vs. 56.95 mg*h/L, p < 0.01) [ 64 ].…”

Aminoglycosides in the Intensive Care Unit: What's New in Population PK Modeling?

“…After assessing the articles for eligibility by applying the inclusion and exclusion criteria, 19 publications were selected. In total, 6, 11, and 5 PopPK models were analyzed for amikacin [16][17][18][19][20][21], gentamicin [21][22][23][24][25][26][27][28][29][30][31] and tobramycin [32][33][34], respectively (Figure 1).…”

“…All 19 studies included in this review used nonlinear mixed effect methods to analyze their data and develop PopPK models. As per Table 2 , a version of NONMEM software was used for the modeling in more than half of the studies (n=10) [19,[22][23][24][25][26][27][32][33][34]. Other software used were NPAG a function from the software Pmetrics (n=2) and the NPEM software (n=2).…”