Article Figures & Data
Figures
- FIG 1
Curve fitting of total ertapenem plasma concentrations in HD patients (n = 11) after multiple-dose regimens. Ertapenem at 500 mg was administered daily to patients via 30-min intravenous infusion. The vertical axis in each diagram indicates the ertapenem plasma level (milligram per liter), and the horizontal axis indicates the time (hours). The observed data are represented by open circles, and the fitted results are depicted with dotted lines. Patients 4 and 6 developed central nervous system toxicity, presenting as self-talking and visual hallucinations, after the seventh and ninth consecutive daily doses of 500 mg ertapenem, respectively.
- FIG 2
Curve fitting of free ertapenem plasma concentrations in HD patients (n = 11) after multiple-dose regimens. Ertapenem at 500 mg was administered daily to patients via 30-min intravenous infusion. The vertical axis in each diagram indicates the ertapenem plasma level (milligram per liter), and the horizontal axis indicates the time (hours). The observed data are represented by open diamonds, and the fitted results are depicted with dotted lines.
- FIG 3
Simulations of ertapenem plasma concentrations. PK parameters for ertapenem obtained from HD patients (n = 11) were used to simulate drug plasma concentrations in a clinical setting. The simulations of total (A) and free (B) ertapenem plasma levels with three different multiple-dose regimens in HD patients were graphed. The shaded regions indicate the standard errors of all concentration points from 11 simulated profiles. Ertapenem was administered via 30-min intravenous infusion at the beginning of each dosing interval. The black lines indicate 500 mg ertapenem administered daily to patients, to follow the current clinical regimen, the blue lines indicate a half dose given daily as current use, and the red lines indicate ertapenem given every other day at a dose of 500 mg. The dotted lines indicate the MICs of ertapenem in total form (10 mg/liter) and free form (2 mg/liter). The levels for all subjects were above the MIC90 therapeutic level (>2 mg/liter) for the entire dosing interval.
- FIG 4
Application of the equations derived from the simulation data to data for another 11 HD patients. The dotted line in each diagram indicates the simulated plasma concentrations of ertapenem following the 500-mg thrice-weekly administration, after each session of HD. The trough concentrations observed for each dosing interval are indicated as open circles. The vertical axis in each diagram indicates the total ertapenem plasma level (milligrams per liter), and the horizontal axis indicates the time (hours). The diagram in the bottom right shows the correlation between observed (Obs) and predicted (Pred) data for patients 12 to 22, using the simulation model.
Tables
- TABLE 1
Basic characteristics and clinical data for infected HD patients who received ertapenem treatment during hospitalization (n = 22)a
↵a All patients were local HD patients in Taiwan.
↵b Kt/V, dialysis efficiency; URR, urea reduction rate; BUN, blood urea nitrogen; Cr, creatinine. Continuous variables are shown as mean ± standard deviation. The normal range for albumin levels is 3.5 to 5.7 mg/dl, that for blood urea nitrogen levels is 7 to 25 mg/dl, and that for creatinine levels is 0.6 to 1.3 mg/dl.
↵c In the reference group, HD patients received ertapenem at 500 mg daily.
↵d In the experimental group, HD patients received ertapenem at 500 mg thrice weekly, after each HD session.
- TABLE 2
Plasma levels of total and free forms of ertapenem and clearance during each HD session for the reference and experimental groups (n = 22)
↵a Times are indicated as mHDn, with m before and n after HD indicating the session of HD and the blood sample collection time during the session of HD, respectively. For example, the first session of HD is indicated by m = 1, and the blood sample collection at the fourth hour of HD is indicated by n = 4. t, plasma level of total ertapenem; mHDt clearance, the plasma level of total ertapenem at 0 h of the m session of HD minus the plasma level of total ertapenem at 4 h of the m session of HD divided by the plasma level of total ertapenem at 0 h of the m session of HD [(mHD0t – mHD4t)/mHD0t]; f, plasma level of the free form of ertapenem; mHDf clearance, the plasma level of the free form of ertapenem at 0 h of the m session of HD minus the plasma level of free ertapenem at 4 h of the m session of HD divided by the plasma level of the free form of ertapenem at 0 h of the m session of HD [(mHD0f – mHD4f)/mHD0f].
