TABLE 1.
Demographics and clinical and biochemical characteristics at day of sampling of patients treated with voriconazole and patients with hypoalbuminemia not treated with voriconazole whose plasma samples were spiked with voriconazole
| Demographic or characteristic | Value(s) or resulta |
||
|---|---|---|---|
| Study A | Study B | Total | |
| Demographics | |||
| No. of patients | 13 | 22 | 35 |
| Median [IQR] age (yrs) | 62 [57.5–71.5] | 66 [60–74] | 65 [58–73] |
| Median [IQR] wt (kg) | 68 [61–82.5] | 71 [60.3–80] | 68 [62–80] |
| No. (%) of males | 7 (53.8) | 14 (63.6) | 21 (60) |
| Mean APACHE II score ± SD | 26.8 ± 6.9 | 23.5 ± 10.0 | 25.3 ± 8.3 |
| No. (%) of cases of in-hospital mortality | 6 (46.2) | 9 (40.9) | 15 (42.9) |
| No. (%) of cases of 28-day mortality | 6 (46.2) | 8 (36.4) | 15 (42.9) |
| Clinical and biochemical characteristics | |||
| Total no. of samples | 20 | 66 | 86 |
| No. (%) of samples from patients with i.v. VRC administrationb | 20 (100) | Not applicable | Not applicable |
| Median [range] albumin plasma concn (g/liter) (35–52)b,e | 31.1 [13.8–38.7] | 23.7 [14.4–33.7] | 26.7 [13.8–38.7] |
| Median [range] AAG plasma concn (g/liter) (0.51–1.17)b,e | 1.8 [1.1–3.0] | 1.4 [0–2.4] | 1.47 [0–3.0] |
| Mean total plasma protein concn ± SD (g/liter) (66–87)b,e | 56.6 ± 7.3 (n = 18) | 53.4 ± 12.4 (n = 63) | 54.2 ± 11.5 |
| Median [IQR] total bilirubin plasma concn (mg/liter) (<1)b,e | 0.41 [0.28–1.69] (n = 12) | 0.75 [0.42–1.93] | 0.67 [0.42–1.80] (n = 85) |
| Median [IQR] blood urea nitrogen (mg/dl) (<50)b,e | 70 [44.8–112.5] | 54.5[37–146] | 57.5 [37–132.5] |
| Median [IQR] creatinine plasma concn (mg/dl) (F, 0.51–0.95; M, 0.67–1.17)b,e | 0.95 [0.52–1.57] | 1.14 [0.67–1.99] (n = 57) | 1.13 [0.67–1.81] (n = 77) |
| CKD-EPI eGFR [ml/(min × 1.73m2)]b | 84 [37.5–108.3] | 66 [40–93] | 74 [40–100] |
| Median [IQR] CRP plasma concn (mg/liter) (<5)b,e | 47.2 [21.6–116.9] | 72.1 [48.2–89.6] | 71.5 [30.8–92.5] |
| Median [IQR] VRC daily dose (mg/day)b | 580 [465–800] | Not applicable | Not applicable |
| Median [IQR] VRC daily dose (mg/kg/day)b | 8 [7.5–8.3] | Not applicable | Not applicable |
| Median [IQR] no. of days of VRC treatment at day of sampling | 6 [4–13] | Not applicable | Not applicable |
| Median [IQR] total VRC plasma concn (mg/liter)b | 2.4 [1.5–4.5] | 1.5; 2.9; 9.0 (spiking expt) | 2.9 [1.5–9.0] |
| Median [IQR] unbound VRC plasma concn (mg/liter) | 0.71 [0.51–1.46] | 0.86 [0.45–2.66] | 0.85 [0.46–2.55] |
| Median [IQR] bound VRC plasma concn (mg/liter) | 1.52 [1.07–2.57] | 1.63 [0.85–5.35] | 1.62 [0.87–5.07] |
| Median [IQR] % protein binding | 49.6 [42.5–52.5] | 49.1 [42.6–52.3] | 49.1 [42.6–52.4] |
| Median [IQR] no. of coadministered drugs with PPB > 70%b | 2.5 [2–3]c | 4.5 [1–6]d | 3 [2–5] |
Study A, patients admitted to the ICU and treated with voriconazole; study B, patients admitted to the ICU and not treated with voriconazole (plasma spiked with 1.5, 2.9, and 9 mg/liter). i.v., intravenous; eGFR, estimated glomerular filtration rate; VRC, voriconazole; CRP, C-reactive protein; AAG, α-1-acid glycoprotein; n, number of samples.
Day of sampling.
In study A, no coadministration of NSAIDs, phenytoin, valproic acid, coumarins, or aspirin was documented.
In study B, administration of aspirin was documented in 7 patients and of acenocoumarol and phenytoin in 1 patient each. No coadministration of NSAIDs or valproic acid was documented.
The values in parentheses represent reference values according to the University Hospitals Leuven.