Table 1.
Characteristics of 46 patients with 207 voriconazole concentrations.
| Patient | Age (y) | Sex | Wt (kg) | Underlying and infectious diagnoses |
EORTC Class [12] |
Died | Dose | No. samples |
Concentration range (ng/mL) |
Total (low) a measured troughs |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 19.5 | F | 84.3 | ALL, relapse Pulmonary aspergillosis | Possible | Yes | 200 mg PO | 16 | 600–2900 | 1 (1) |
| 2 | 17.4 | M | 85.7 | ALL, BMT Alternaria spp. sinusitis | Probable | No | 300 mg PO | 1 | 5300 | 1 (0) |
| 3 | 4.5 | M | 18.2 | Liver transplant Pulmonary aspergillosis | Possible | No | 75 mg PO | 2 | 400–500 | 0 (0) |
| 4 | 13.9 | M | 45.8 | ALL, BMT Pneumonia | Possible | No | 200 mg PO | 1 | 1700 | 0 (0) |
| 5 | 15.5 | F | 75.4 | Lymphoma, relapse Pneumonia | Possible | No | 200 mg PO | 1 | 200 | 0 (0) |
| 6 | 8.3 | F | 47.8 | Hemophagocytic lymphocytic histiocytosis Disseminated candidiasis, sinusitis | Possible | Yes | 180 mg IV | 3 | 400–6700 | 1 (1) |
| 7 | 14.5 | M | 65.0 | ALL, relapse Pulmonary aspergillosis | Possible | Yes | 200 mg PO | 1 | 7900 | 0 (0) |
| 8 | 6.3 | M | 20.0 | Aplastic anemia Brain abscesses | Possible | No | 150–200 mg PO | 5 | 1300–2600 | 2 (0) |
| 9 | 0.8 | M | 8.8 | CGD Aspergillus versicolor pneumonia and osteomyelitis | Proven | No | 36–72 mg PO | 18 | BLQ-4400 | 0 (0) |
| 10b | 12.8 | M | 29.0 | CF ABPA | Possible | Yes | 60 mg PO | 1 | 1000 | 0 (0) |
| 11 | 16.5 | F | 47.3 | AML, BMT Candida glabrata esophagitis | Proven | No | 200 mg PO | 1 | 200 | 1 (1) |
| 12 | 20.0 | M | 54.2 | CNS Germ cell tumor Aspergillus fumigatus brain abscess | Proven | No | 350–600 mg PO | 5 | 2300–21300 | 1 (0) |
| 13b | 18.1 | M | 56.1 | Liver transplant Scedosporium apiospermum osteomyelitis | Proven | No | 200 mg PO | 1 | BLQ | 0 (0) |
| 14b | 19.7 | M | 77.3 | None Coccidioidomyces imitis meningitis | Proven | No | NR | 3 | 300–500 | 0 (0) |
| 15 | 7.7 | M | 35.4 | CGD Pulmonary aspergillosis | Possible | No | 300 mg PO | 1 | 3500 | 1 (0) |
| 16 | 5.3 | F | 20.8 | ALL, relapse Pulmonary aspergillosis | Possible | No | 130 mg PO | 1 | 2300 | 1 (0) |
| 17 | 16.0 | F | 58.6 | ALL, relapse Disseminated candidiasis | Possible | No | 200 mg PO | 1 | 6000 | 0 (0) |
| 18 | 9.5 | F | 21.4 | Aplastic anemia, BMT Pulmonary aspergillosis | Possible | Yes | 80–140 mg IV | 3 | 800–2800 | 1 (1) |
| 19 | 20.5 | F | 49.2 | SLE Aspergillus niger pneumonia | Probable | No | 200 mg PO | 1 | 200 | 1 (1) |
| 20 | 11.9 | F | 42.0 | CGD Pulmonary aspergillosis | Proven | Yes | 200–250 mg PO | 21 | BLQ-11900 | 1 (1) |
| 21 | 1.0 | M | 7.9 | CGD Pneumonia | Possible | No | 30 mg PO | 1 | 3000 | 1 (0) |
| 22 | 9.3 | F | 22.3 | AML, relapse Disseminated Candida glabrata | Possible | Yes | 100–150 mg PO | 4 | BLQ-4200 | 0 (0) |
| 23 | 7.5 | M | 21.0 | CF Aspergillus fumigatus pneumonia | Proven | No | 90–270 mg PO | 5 | BLQ-13200 | 2 (0) |
| 24 | 18.2 | M | 50.1 | Lung sarcoma Pulmonary aspergillosis | Proven | No | 200–400 mg NG | 3 | 1900-10500 | 1 (0) |
| 25 | 11.0 | F | 34.0 | ALL, relapse Disseminated candidiasis | Possible | Yes | 150–300 mg PO | 8 | BLQ-7500 | 1 (0) |
| 26 | 19.7 | M | 44.0 | CF, Lung transplant Aspergillus fumigatus sinusitis | Proven | No | 200–400 mg PO | 9 | BLQ-10900 | 1 (0) |
| 27 | 17.0 | F | 58.3 | ALL Pulmonary aspergillosis | Possible | No | 200 mg PO | 2 | 2700–5300 | 0 (0) |
| 28 | 14.0 | M | 47.9 | CF Aspergillus versicolor and terreus pneumonia | Probable | No | 200–300 mg PO | 3 | BLQ-700 | 0 (0) |
| 29 | 12.1 | M | 48.3 | ALL Disseminated candidiasis | Possible | No | 200 mg PO | 5 | 1800–5800 | 1 (0) |
| 30 | 8.8 | M | 20.6 | ALL, relapse Pulmonary aspergillosis | Probable | Yes | 75–200 mg PO | 8 | 300–3300 | 2 (2) |
| 31 | 3.0 | F | 14.4 | ALL Disseminated candidiasis | Proven | Yes | 55–150 mg IV/PO | 3 | BLQ-700 | 0 (0) |
| 32 | 14.6 | M | 31.8 | CF ABPA | Possible | No | 150–200 mg PO | 2 | 1900–3200 | 1 (0) |
| 33 | 15.7 | M | 90.0 | ALL Disseminated candidiasis | Possible | No | 200 mg PO | 2 | 600–2800 | 0 (0) |
| 34 | 2.6 | M | 19.4 | ALL high risk, refractory Disseminated Scedosporium apiospermum | Proven | Yes | 50–140 mg PO | 2 | 200–3000 | 2 (1) |
| 35 | 2.9 | M | 14.3 | SCID, BMT Disseminated aspergillosis | Probable | Yes | 55–150 mg IV | 5 | 300–600 | 1 (1) |
| 36 | 7.4 | F | 24.8 | CF ABPA | Possible | No | 150 mg IV | 4 | BLQ-2700 | 0 (0) |
| 37 | 12.7 | M | 37.8 | ALL, relapse Brain abscess | Possible | Yes | 160 mg IV | 2 | BLQ-1000 | 0 (0) |
| 38 | 9.9 | M | 22.1 | CF, liver transplant Pulmonary aspergillosis and Scedosporium apiospermum pneumonia | Probable | No | 95–250 mg PO | 10 | BLQ-18000 | 1 (0) |
| 39 | 9.2 | F | 20.2 | CF Pulmonary aspergillosis | Possible | No | 140 mg PO | 3 | 1100–2600 | 0 (0) |
| 40 | 17.6 | M | 55.5 | SLE Aspergillosis | Possible | No | 200 mg PO | 1 | 200 | 0 (0) |
| 41 | 4.4 | M | 16.8 | Lymphoma Disseminated candidiasis | Possible | No | 110 mg IV | 1 | 1100 | 0 (0) |
| 42b | 4.6 | M | 14.3 | Toxic epidermal necrosis Cutaneous Aspergillus niger | Proven | No | 100 mg IV | 2 | BLQ | 0 (0) |
| 43b | 17.8 | M | 59.8 | CF, lung transplant Aspergillus versicolor pneumonia | Probable | No | 300–400 mg PO | 5 | 900–5900 | 0 (0) |
| 44 | 7.9 | M | 27.2 | CGD Pneumonia | Possible | No | 250 mg PO | 17 | BLQ-12400 | 0 (0) |
| 45b | 14.4 | M | 29.0 | CGD Pneumonia | Possible | No | NR | 4 | 300–2500 | 0 (0) |
| 46 | 1.4 | F | 11.9 | ALL, BMT Pneumonia | Possible | No | 40–120 mg PO | 9 | 500–3600 | 7 (3) |
| Median or percent | 12.0 y | M 65% | 33.3 kg | Proven 26% | Died 28% | IV 150 mg 6.0 mg/kg | 3 | 2,100 ng/mL | ||
| F 35% | Probable 44% | PO/NG 200 mg 5.3 mg/kg | ||||||||
| Possible 59% | ||||||||||
| Range | 0.8– 20.5 | 6.5– 102.2 | IV 55–180 mg 3.4–10.5 mg/kg | 1–21 | BLQ (n=23) - 21,300 ng/mL | |||||
| PO/NG 30–600 mg 2.0–12.9 mg/kg |
Abbreviations: ALL=Acute Lymphoblastic Leukemia; AML=Acute Myelogenous Leukemia; BMT=Bone Marrow Transplant; CGD=Chronic Granulomatous Disease; CF=Cystic Fibrosis; CNS=Central Nervous System; BLQ=Below the Limit of Quantification; NR=Not recorded
Notes:
a
Total number of samples obtained at least 10 hours after previous dose and subset of these with voriconazole <1,000 ng/mL
b
These patients were excluded from the population model as all measured concentrations were either BLQ, not after a dose with a verified time (i.e. outpatient), or after an unverified dose amount. The remaining patients may have had some measurements excluded for the same reasons, but had at least one valid sample available for modeling.