Amikacin Population Pharmacokinetics in Critically Ill Kuwaiti Patients

Abstract

Amikacin pharmacokinetic data in Kuwaiti (Arab) intensive care unit (ICU) patients are lacking. Fairly sparse serum amikacin peak and trough concentrations data were obtained from adult Kuwaiti ICU patients. The data were analysed using a nonparametric adaptive grid (NPAG) maximum likelihood algorithm. The estimations of the developed model were assessed using mean error (ME) as a measure of bias and mean squared error (MSE) as a measure of precision. A total of 331 serum amikacin concentrations were obtained from 56 patients. The mean (±SD) model parameter values found were V c = 0.2302 ± 0.0866 L/kg, k slope = 0.004045 ± 0.00705 min per unit of creatinine clearance, k 12 = 2.2121 ± 5.506 h−1, and k 21 = 1.431 ± 2.796 h−1. The serum concentration data were estimated with little bias (ME = −0.88) and good precision (MSE = 13.08). The present study suggests that amikacin pharmacokinetics in adult Kuwaiti ICU patients are generally rather similar to those found in other patients. This population model would provide useful guidance in developing initial amikacin dosage regimens for such patients, especially using multiple model (MM) dosage design, followed by appropriate Bayesian adaptive control, to optimize amikacin dosage regimens for each individual patient.

Amikacin in Critically Ill Patients: A Review of Population Pharmacokinetic Studies

“…However, only ten models have been described for amikacin in critically ill patients, using a nonlinear mixedeffects model [19][20][21][22][23][24][25][26][27][28]. Amikacin pharmacokinetics have been described by mono-exponential models as well as by bi-exponential models.…”

“…Among these, 23 were excluded with reference to the inclusion and exclusion criteria. A total of ten articles were finally retained after three additional trials were added from reference scanning [19][20][21][22][23][24][25][26][27][28] (Fig. 1).…”

“…The studied populations consisted of critically ill patients with suspected Gram-negative infection, mainly septicaemia, pneumonia or severe trauma. Amikacin was administered as intermittent infusions according to different dosing regimens: once-daily dosing, twice-daily dosing or a dose interval adjusted according to a pharmacokinetic dosing method [19][20][21][22][23][24][25][26][27][28]. The doses administered ranged between 7.5 and 30 mg/kg/day ( ---data resulted in therapeutic drug monitoring.…”

Novel Approach To Optimize Synergistic Carbapenem-Aminoglycoside Combinations against Carbapenem-Resistant Acinetobacter baumannii

“…4D). This highlights the importance of evaluating the robustness of combination dosage regimens via Monte Carlo simulations in the presence of the large between-patient variability in pharmacokinetics (17,19,53,54).…”

Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling

“…Yadav et al Antimicrobial Agents and Chemotherapy tion dosage regimens for effective early therapy via Monte Carlo simulations in the presence of the high between-patient variability in PK that is typically observed in critically ill patients (41)(42)(43). Our most robust regimen, which contained imipenem at 5 g/day as a continuous infusion, was promising with regard to success rate of therapy; however, this dose may slightly increase the risk of seizures compared to that with 2 to 4 g imipenem per day (44,45).…”