The area under the serum amikacin concentration-time curve after the first dose (AUC0-12 http://www.selleckchem.com/products/Bosutinib.html hour) was calculated from the experimental data points obtained after the first dose on day 3 (30 minutes, and 1, 3, 6, 9 and 12 hours) using the trapezoidal method.To determine amikacin absorption during the study period, amikacin concentrations were measured in the two day 3 urine collections, which reflected the quantity of each 12-hour dose absorbed via inhalation.Because day 3 tracheal aspirates were not collected at specific time points, the 24-hour collection time was divided into four equivalent six-hour periods and then all results obtained during the corresponding period were pooled.

The first period (H1 to H6) corresponds to the first six hours following the first day 3 aerosol, the second (H7 to H12) to the next six hours (before the second aerosol of the day), the third (H13 to H18) to the six hours following the second day 3 nebulization, and the fourth (H19 to H24) to the last six hours of the day, before the next aerosol.All results are expressed as medians (interquartile range (IQR)), unless specified otherwise.ResultsThe characteristics of the 30 patients included in this study are reported in Table Table1;1; 28 patients with VAP were included (no patients with HAP or HCAP were included) in the pharmacokinetic study after the specimens from two patients were excluded because these patients did not meet the requirement of receiving at least three full days of study medication to be included.

All these 28 patients were on mechanical ventilation at day 3 (both nebulization of day 3), either through an endotracheal tube or a tracheotomy. Throughout the study, the median (IQR) duration of nebulization was 36 (30 to 45) minutes for intubated patients on mechanical ventilation. Median (IQR) duration of the 22 nebulizations for extubated patients using the handheld device was 20 (20 to 25) minutes.Table 1Characteristics of the 30 patients with Gram-negative VAP*The median day 3 serum amikacin concentrations for the 28 patients are shown in Figure Figure2.2. Median (IQR) Cmax and Tmax were 0.85 (0.67 to 1.01) ��g/mL and 1.0 (1 to 3) hours, respectively. AUC0-12 hour for amikacin was 6.15 (4.73 to 9.57) ��g.hr/mL. The median total amount of amikacin excreted in urine during the first and second 12-hour specimens were 19 (12.21 to 28) and 21.2 (14.

1 to 29.98) ��g, respectively.Figure 2Day 3 serum amikacin concentrations before (0), and at hours 0.5, 1, 3, 6, 9, 12, 13 and 24 after starting the first aerosol. Results are expressed as medians (interquartile range). Black arrows indicate Carfilzomib the timing of aerosols.Fifteen to 30 minutes after the end of nebulization on day 3, the median amikacin concentration in ELF was 976.07 (410.33 to 2563.12) ��g/mL, with respective lower and upper values of 135.67 and 16,127.56 ��g/mL (Figure (Figure3).3). Median VELF was 0.46 (0.27 to 0.86) mL.