2.7. Application of the Method to Pharmacokinetic Studies

We evaluated the applicability of the method for PK studies by analyzing plasma samples collected from two critically ill patients diagnosed with pneumonia and treated with ceftaroline fosamil (600 mg every 8 h) after positive cultures of methicillin-resistant Staphylococcus aureus (MRSA). Blood samples were collected in K₂EDTA tubes and centrifuged at 5000× g for 10 min. Plasma samples were stored at −80 °C until analysis and were analyzed within three weeks of extraction. Table 2 shows data from ceftaroline-treated patients. The study was conducted among critically ill patients admitted to the ICUs of Araba University Hospital (Vitoria-Gasteiz, Spain). Informed consent was obtained from both subjects involved in the study.

Data for the critically ill patients.

APACHE: acute physiology and chronic health evaluation; MIC: minimum inhibitory concentration.

From the plasma concentrations of ceftaroline in the patients, we obtained the individual pharmacokinetic parameters through a non-compartmental analysis. For this purpose, we used the software Phoenix 64 (Build 8.1.3530, Certara USA, Inc., Princeton, NJ, USA). The elimination rate constant (Ke) was obtained by log-linear regression analysis of the terminal phase of the plasma drug concentration–time curve. The half-life (t_1/2) was obtained by using the following equation: t_1/2 = ln(2)/ke. The area under the plasma concentration–time curve from the first to the last concentration measured (AUCτ) was calculated with the linear trapezoidal method. The total body clearance (CL_T) was obtained with the following equation: CL_T = dose/AUCτ. The mean residence time (MRT) was obtained through the equation: MRT = AUMCτ/AUCτ, where AUMCτ is the area under the moment curve. Finally, the distribution volume at steady-state (Vss) was estimated with the following equation: Vss = CL_T × MRT.