TABLE 2.
Concentrations of radioactivity in tissues and fluids determined by QWBA at specified times after oral administration of [cyano-14C]isavuconazonium sulfate for up to 21 consecutive days in male albino ratsb
| Matrix | Concn of [cyano-14C]isavuconazonium sulfate (μg eq/g) at the indicated times after the last dose on: |
|||||||
|---|---|---|---|---|---|---|---|---|
| Day 1 |
Day 7 |
Day 14 |
||||||
| 1 h | 4 h | 8 h | 24 h | 1 h | 24 h | 1 h | 24 h | |
| Adrenal cortex | 10.1a | 24.1a | 19.0a | 6.54a | 20.9a | 14.3a | 23.1a | 16.9a |
| Adrenal gland(s) | 9.51a | 22.7a | 17.1a | 5.83a | 19.3a | 12.4a | 21.2a | 14.0a |
| Adrenal medulla | 8.04a | 17.9a | 10.8a | 3.47a | 11.7a | 6.37a | 19.2a | 5.12a |
| Aorta | 2.00 | 4.67 | 3.76 | ND | 2.75 | 1.51 | 4.53 | 2.35 |
| Arterial wall | ND | 5.53 | ND | ND | 1.88 | ND | 3.43 | ND |
| Bile | 101 | 198 | 109 | 27.3 | 472 | 27.7 | 157 | ND |
| Blood | 0.783 | 1.99 | 1.81 | ND | 1.70 | 1.34 | 3.04 | 1.41 |
| Bone | BLQ | BLQ | BLQ | ND | BLQ | BLQ | BLQ | BLQ |
| Bone marrow | 2.35 | 4.23 | 3.41 | ND | 1.90 | 0.979 | 4.03 | BLQ |
| Brain cerebellum | 1.55 | 3.28 | 2.11 | ND | 1.81 | BLQ | 2.74 | BLQ |
| Brain cerebrum | 1.51 | 3.36 | 2.02 | ND | 1.86 | BLQ | 2.72 | BLQ |
| Brain medulla | 1.60 | 3.52 | 2.22 | ND | 1.79 | BLQ | 2.93 | BLQ |
| Brain olfactory lobe | 1.46 | 2.93 | 1.70 | ND | 1.44 | BLQ | 2.46 | BLQ |
| Bulbourethral gland | 2.21 | 6.14 | 4.67 | ND | 3.08 | 0.933 | 4.60 | 1.27 |
| Cecum | BLQ | 12.9 | 9.22 | 7.13 | 6.41 | 6.57 | 13.5 | 13.6 |
| Cecum mucosa | 4.12 | 15.8 | 13.7 | 7.42 | 16.6 | 11.4 | 18.2 | 10.9 |
| Diaphragm | 2.86 | 5.22 | 3.97 | BLQ | 3.52 | 0.920 | 5.01 | 1.27 |
| Epididymis | 1.00a | 4.88 | 3.07 | ND | 1.57 | 0.819a | 2.26a | 0.925a |
| Esophagus | 3.00 | 4.44 | 2.51 | 0.896 | 2.10 | 1.19 | 2.89 | BLQ |
| Exorbital lacrimal gland | 3.62 | 9.17 | 7.04 | 0.881 | 3.94 | 1.37 | 6.64 | 1.21 |
| Eye lens | BLQ | BLQ | BLQ | ND | BLQ | BLQ | BLQ | BLQ |
| Eye uveal tract | 1.21 | 2.40 | 1.31 | ND | 1.39 | 1.06 | 2.16 | 0.948 |
| Eye(s) | BLQ | BLQ | BLQ | ND | BLQ | BLQ | 0.787 | BLQ |
| Fat (brown) | 5.34 | 8.80 | 8.56 | 0.939 | 7.00 | 1.69 | 9.92 | 2.20 |
| Fat (mesenteric) | 0.802 | 23.4 | 21.0 | 1.80 | 2.96 | 2.21 | 1.17 | 2.67 |
| Fat (reproductive) | BLQ | 16.0 | 15.5 | 2.27 | 3.76 | 3.66 | 2.03 | 3.73 |
| Fat (white) | 1.74 | 26.7 | 16.8 | 1.59 | 2.53 | 2.20 | 2.39 | 1.42 |
| Harderian gland | 3.63 | 12.6 | 9.14 | 1.03 | 4.55 | 1.73 | 6.58 | 1.38 |
| Intra-orbital lacrimal gland | 3.34 | 7.94 | 6.51 | ND | 3.38 | 1.39 | 6.77 | 1.33 |
| Kidney cortex | 4.67 | 10.4 | 6.96 | ND | 6.60 | 2.42 | 9.24 | 2.73 |
| Kidney medulla | 4.64 | 9.76 | 6.43 | ND | 6.10 | 2.43 | 9.31 | 2.33 |
| Kidney(s) | 4.65 | 10.2 | 6.80 | 1.42 | 6.46 | 2.43 | 9.29 | 2.58 |
| Large intestine | BLQ | 3.25 | 4.05 | 1.91 | 3.49 | 1.90 | 4.00 | 1.46 |
| Large intestine mucosa | 2.55 | 4.80 | 2.88 | 1.92 | 3.21 | 4.06 | 5.32 | 2.31 |
| Liver | 35.8 | 38.3 | 31.5 | 7.53 | 40.1 | 15.6 | 58.8 | 18.4 |
| Lung(s) | 2.03 | 4.61 | 3.49 | 0.757 | 3.13 | 1.41 | 3.14 | 1.16 |
| Lymph node(s) | 1.22 | 3.57 | 3.02 | ND | 2.06 | 0.987 | 2.80 | 1.12 |
| Lymph node(s), mandibular | 1.35 | 3.61 | 2.78 | ND | 1.82 | ND | 2.96 | ND |
| Muscle | 1.32 | 3.64 | 2.43 | BLQ | 1.59 | BLQ | 1.84 | BLQ |
| Myocardium | 3.10 | 6.79 | 4.32 | 0.964 | 3.99 | 1.49 | 5.60 | 1.83 |
| Nasal mucosa | 1.36 | 6.08 | 3.64 | 0.895 | 1.98 | 1.19 | 3.17 | 1.76 |
| Pancreas | 3.99 | 8.09 | 5.77 | 0.749 | 4.20 | 1.05 | 6.34 | 1.17 |
| Pineal body | 1.84 | 5.31 | 3.93 | ND | 4.13 | ND | 4.47 | ND |
| Pituitary gland | 2.50 | 4.61 | 2.80 | ND | ND | ND | 4.85 | ND |
| Preputial gland | ND | 8.32a | 12.0a | ND | 4.00a | 3.12a | 4.52a | 2.20a |
| Prostate gland | 2.78 | 13.0 | 5.39 | BLQ | 3.24 | 1.10 | 3.23 | 1.17 |
| Rectum mucosa | 0.989 | 2.61 | 2.00 | 0.821 | 1.75 | 0.778 | 1.55 | 1.30 |
| Salivary gland(s) | 2.91 | 5.91 | 4.29 | BLQ | 3.56 | 0.868 | 5.03 | 0.941 |
| Seminal vesicle(s) | BLQ | 3.32 | 1.62 | BLQ | 1.97 | 0.783 | 1.63 | 0.938 |
| Skin (nonpigmented) | 1.06 | 3.64 | 3.33 | BLQ | 1.87 | 0.988 | 2.16 | 1.01 |
| Small intestine | 1.74 | 4.50 | 12.9 | 3.65 | 9.95 | 3.07 | 10.0 | 2.57 |
| Small intestine mucosa | 3.15 | 14.6 | 21.7 | 7.81 | 16.7 | 7.26 | 21.9 | 9.43 |
| Spinal cord | 1.41 | 3.74 | 2.16 | ND | 1.80 | ND | 2.92 | BLQ |
| Spleen | 2.12 | 3.68 | 3.28 | ND | 2.47 | 1.00 | 4.02 | 1.11 |
| Stomach | 4.31 | 5.10 | 4.41 | BLQ | 4.74 | 1.56 | 5.93 | 1.11 |
| Stomach mucosa | 5.48 | 7.97 | 6.16 | ND | 6.27 | ND | 9.00 | ND |
| Stomach wall | 1.57 | 2.61 | 1.98 | ND | 3.19 | ND | 2.43 | ND |
| Testis(es) | 1.01 | 3.21 | 2.28 | BLQ | 1.50 | 0.882 | 2.26 | 1.00 |
| Thymus | 1.42 | 2.86 | 2.03 | BLQ | 1.53 | BLQ | 2.26 | BLQ |
| Thyroid | 2.15 | 5.39 | 3.76 | ND | 4.88 | 2.08 | 5.23 | 2.52 |
| Tongue | 2.43 | 5.70 | 3.59 | BLQ | 3.22 | 0.927 | 4.27 | 0.970 |
| Tooth pulp | 1.23 | 2.50 | 1.71 | ND | 1.67 | 1.07 | 3.07 | 0.884 |
| Urinary bladder | 5.39 | 9.97 | 3.69 | 3.77 | 4.79 | 1.71 | 2.67 | 12.8 |
| Urine | 8.85 | 119 | 102 | 9.75 | 16.6 | 16.4 | 58.0 | 20.4 |
a
Tissue appeared to be fat soaked.
b
[cyano-14C]isavuconazonium sulfate was administered at 30 mg/kg/day. BLQ, below the limit of quantitation (the lower limit of quantitation for day 1 was <0.742 μg eq [cyano-14C]isavuconazonium sulfate/g; the lower limit of quantitation for days 7 and 14 was <0.748 μg eq [cyano-14C]isavuconazonium sulfate/g); ND, not detectable (the borders of the sample were not discernible from the background or surrounding tissue); QWBA, quantitative whole-body autoradiography.