Article Figures & Data
Figures
- FIG 1
Caspofungin plasma concentration-time curves on day 5 in patients receiving the 50-mg maintenance dose (A) and the 70-mg maintenance dose (B).
- FIG 2
Elimination rate constants, k10, on day 5 at different C-P levels (n = 37). Horizontal bars demonstrate median values.
- FIG 3
Correlation plot between AUC0–24 and albumin levels on day 5 (n = 37). The two patients with low AUC0–24 despite the highest albumin levels were the two classified as C-P class A with a score of 5 and associated with high elimination rates, as demonstrated in Fig. 4. Correlation analysis restricted to patients with C-P class B resulted in an r value of 0.51 (P = 0.002; n = 35).
- FIG 4
Proportion of patients on day 5 reaching target concentrations for Candida albicans (A) and C. glabrata (B) with different MICs. The distribution of the MIC values for C. albicans and C. glabrata are included at the top. Similar results were found on days 2 and 10. AUC/MIC ratios for C. albicans and C. glabrata of 865 and 450, respectively, were used in the calculations and refer to Andes et al. (32). The MIC distributions were obtained from Pfaller et al. (21).
- FIG 5
Pharmacokinetic two-compartment model. The central compartment (V1) represents blood and well-perfused organs, and the peripheral compartment (V2) represents more poorly perfused tissues. k12 and k21 are rate constants between V1 and V2, and k10 is the elimination rate constant from V1. k10 represents the fraction of caspofungin eliminated per hour from V1 at equilibrium between V1 and V2.
Tables
- TABLE 1
Demographic and other characteristics of included patientsc
Parameter Value(s) Demographics No. male/no. female (%) 35/11 (76/24) Age [yr; median (range)] 64 (19–89) Weight [kg; median (range)] 80 (50–114) No. with weight of ≤80 kg 23 No. with weight of >80 kg 23 BMI [kg/m²; median (range)] 25.1 (16.0-43.5) ICU, n Surgical and medical 24 Cardiothoracic 19 Burn 3 Primary diagnosis at admission to ICU, n Cardiac arrest 3 Cardiothoracic surgery 8 Pulmonary disease 8 Aortic surgery 5 Abdominal surgery or pancreatitis 4 Kidney transplantation 1 Hematological malignancies 3 Burn injury 4 Primary infection 10 APACHE II score, n (range) 19 (3–40) Indication for treatment,a n (%) Candidemia 3 (7) Abdominal candidiasis 5 (11) Empirical 37 (80) Prophylaxis 1 (2) Species, nb C. albicans 27 C. glabrata 1 C. parapsilosis 3 Yeast; not specified 1 Mixed 8 C. albicans 5 C. glabrata 4 C. parapsilosis 4 C. tropicalis 1 C. lusitaniae 1 C. guilliermondii 1 - TABLE 2
Child-Pugh score, SOFA score, vital organ support, and parameters of hepatic and renal functiona
Parameter Value(s) on day: 2 (n = 46) 5 (n = 37) Child-Pugh, n (%) Score 5 2 (4) 2 (5) Score 6 3 (7) 0 Score 7 25 (54) 24 (65) Score 8 3 (7) 6 (16) Score 9 12 (26) 5 (14) Score 10 1 (2) 0 Class A 5 (11) 2 (5) Class B 40 (87) 35 (95) Class C 1 (2) 0 SOFA score, median (range) 9 (2–21) 7 (2–17) Vital organ support, n (%) CRRT 21 (45) 15 (40) Ventilator 41 (89) 30 (81) ECMO 9 (20) 9 (20) Parameters of hepatic and
renal function, median (range)P-bilirubin, μmol/liter 24 (4–286) 18 (4–296) P-albumin, g/liter 18.5 (11–44) 20 (12–39) P-INR 1.2 (0.9–1.8) 1.2 (1.0–1.7) P-ALT, μkat/liter 0.64 (0.15–10.5) 0.86 (0.15–8.0) P-ALP, μkat/liter 1.7 (0.59–8.6) 1.8 (0.9–8.0) P-creatinine, μmol/liter 97 (29–550) 96 (36–289) GFR, ml/min/1.73m² 84b (23–116) 89c (25–117) ↵a Values are given in absolute numbers (percent) or median (range). SOFA score, sequential organ failure assessment score; CRRT, continuous renal replacement therapy mainly performed as continuous venovenous hemodialysis; ECMO, extracorporeal membrane oxygenation; P, plasma; INR, international normalized ratio; ALT, alanine aminotransferase; ALP, alkaline phosphatase; μkat/liter, microkatal/liter; GFR, glomerular filtration rate as estimated by the Modification of Diet in Renal Disease Study equation.
↵b Twenty-five patients (patients with CRRT excluded).
↵c Twenty-two patients (patients with CRRT excluded).
- TABLE 3
PK parameters estimated by using all data or specific data
Parametera PK values [median (range)] for: All data (n = 46) Day 2 (n = 46) Day 5 (n = 37) Day 10 (n = 21) Cmax (mg/liter) 5.1 (1.1–8.8) 5.6 (3.6–9.0) 5.3 (3.6–9.4) Cmin (mg/liter) 1.1 (0.5–2.3) 1.2 (0.5–2.7) 1.1 (0.5–2.6) AUC0-24 (mg·h/liter) 59.6 (32.7–105) 61.1 (32.8–108) 57.8 (44.0–113) 58.4 (37.2–105) CL (liters/h) 0.87 (0.47–1.70) 0.84 (0.46–1.78) 0.88 (0.44–1.58) 0.90 (0.47–1.88) V1 (liters) 11.2 (6.7–26.4) 11.2 (6.7–26.4) 11.9 (7.5–20.1) 11.2 (7.7–19.4) V2 (liters) 6.9 (1.6–22) 6.9 (2.6–13) 5.3 (1.5–7.1) 5.5 (3.3–6.6) k10 (/h) 0.074 (0.047–0.11) 0.072 (0.048–0.11) 0.079 (0.054–0.12) 0.077 (0.061–0.12) ↵a Cmax, maximal concentration; Cmin, minimal concentration; AUC0–24, area under the concentration-time curve from 0 to 24 h; CL, clearance; V1, central volume of distribution; V2, peripheral volume of distribution; k10, elimination rate constant from V1 at equilibrium between V1 and V2. Shrinkage (%): all data, CL of 11.2, V1 of 9.3, and V2 of 33.7; day 2, CL of 2.6, V1 of 4.6, and V2 of 54.0; day 5, CL of 17.6, V1 of 28.9, and V2 of 63; day 10, CL of 11.5, V1 of 42.1, and V2 of 76.7.
- TABLE 4
Correlation coefficients between PK parameters and Child-Pugh score, plasma bilirubin, albumin, INR, and SOFA score on day 5a (n = 37)
Parameter AUC0-24 CL V1 k10 C-P score 0.03 −0.07 0.19 −0.50** Bilirubin 0.00 0.02 0.22 −0.46** Albumin 0.45** −0.31 −0.15 −0.34* INR −0.08 0.00 −0.03 −0.04 SOFA score 0.03 −0.05 0.20 −0.47** ↵a C-P, Child-Pugh; INR, international normalized ratio; SOFA, sequential organ failure assessment; AUC0–24, area under the concentration-time curve from 0 to 24 h; V1, central volume of distribution; V2, peripheral volume of distribution; k10, the elimination rate constant from V1 at equilibrium between V1 and V2. *, P < 0.05. **, P < 0.01.
Supplemental material
- Supplemental file 1 -
Supplemental material
PDF, 614K
- Supplemental file 1 -
