TABLE 3.
Concentrations of radioactivity in tissues and fluids determined by QWBA at specified times after oral administration of [cyano-14C]isavuconazonium sulfate for 21 consecutive days in male albino ratse
| Matrix | Concn of [cyano-14C]isavuconazonium sulfate (μg eq/g) at: |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| Predosea | 1 ha | 4 ha | 8 ha | 24 ha | 72 ha,b | 168 ha | 336 ha | 672 ha | |
| Adrenal cortex | 17.2c | 22.8c | 33.6c | 26.4c | 12.7c | 10.4 | 4.45c | 2.43c | 1.29 |
| Adrenal gland(s) | 14.3c | 20.7c | 29.2c | 22.4c | 11.4c | 7.78 | 3.81c | 2.14c | 1.13 |
| Adrenal medulla | 6.86c | 8.12c | 13.3c | 10.5c | 7.21c | 3.41 | 1.94c | 1.02c | BLQ |
| Aorta | 1.20 | 4.22 | 6.37 | 3.44 | ND | ND | ND | ND | ND |
| Arterial wall | ND | ND | 6.91 | 3.12 | ND | ND | ND | ND | ND |
| Bile | 37.6 | 186 | 231 | 194 | 25.3 | ND | ND | ND | ND |
| Blood | 1.21 | 2.60 | 3.73 | 2.18 | 1.01 | BLQ | BLQ | BLQ | ND |
| Bone | BLQ | BLQ | BLQ | BLQ | BLQ | ND | ND | ND | ND |
| Bone marrow | 0.975 | 3.24 | 7.10 | 2.34 | BLQ | ND | ND | ND | ND |
| Brain cerebellum | BLQ | 2.59 | 5.15 | 1.70 | BLQ | ND | ND | ND | ND |
| Brain cerebrum | BLQ | 2.66 | 5.45 | 1.68 | BLQ | ND | ND | ND | ND |
| Brain medulla | 0.813 | 2.79 | 5.45 | 1.88 | BLQ | ND | ND | ND | ND |
| Brain olfactory lobe | BLQ | 2.34 | 4.52 | 1.69 | BLQ | ND | ND | ND | ND |
| Bulbourethral gland | 1.24 | 4.27 | 6.78 | 3.36 | 0.788 | ND | ND | ND | ND |
| Cecum | 8.39 | 9.97 | 24.0 | 21.2 | ND | 1.08 | BLQ | ND | ND |
| Cecum mucosa | 20.1 | 16.6 | 43.7 | 40.5 | ND | ND | ND | ND | ND |
| Diaphragm | 1.13 | 3.84 | 7.51 | 3.09 | 0.753 | 0.764 | BLQ | ND | ND |
| Epididymis | 0.998c | 2.22 | 5.93c | 3.09c | BLQc | BLQ | BLQ | ND | ND |
| Esophagus | 0.928 | 2.52 | 4.29 | 2.59 | BLQ | BLQ | ND | ND | ND |
| Exorbital lacrimal gland | 1.26 | 5.60 | 11.2 | 5.04 | 1.20 | BLQ | BLQ | BLQ | ND |
| Eye lens | BLQ | 0.794 | 1.35 | 0.830 | BLQ | ND | ND | ND | ND |
| Eye uveal tract | BLQ | 2.22 | 4.58 | 2.20 | 1.17 | ND | ND | ND | ND |
| Eye(s) | BLQ | BLQ | 1.28 | 0.775 | BLQ | ND | ND | ND | ND |
| Fat (brown) | 2.30 | 9.33 | 17.7 | 8.62 | 1.50 | 1.19 | 1.11 | BLQ | ND |
| Fat (mesenteric) | 1.46 | 3.43 | 18.7 | 7.62 | 2.33 | 0.781 | BLQ | ND | ND |
| Fat (reproductive) | 3.59 | 3.62 | 10.9 | 8.01 | 2.99 | BLQ | BLQ | BLQ | ND |
| Fat (white) | 1.46 | 2.75 | 12.1 | 7.97 | 1.04 | 0.830 | BLQ | ND | ND |
| Harderian gland | 1.50 | 6.58 | 18.9 | 7.23 | 1.06 | ND | ND | ND | ND |
| Intra-orbital lacrimal gland | 1.39 | 5.89 | 11.0 | 5.36 | 1.32 | ND | ND | ND | ND |
| Kidney cortex | 2.64 | 8.76 | 16.1 | 7.53 | 2.33 | 1.64 | 1.05 | 0.969 | BLQ |
| Kidney medulla | 2.69 | 8.49 | 12.3 | 7.02 | 1.97 | 1.29 | BLQ | BLQ | BLQ |
| Kidney(s) | 2.64 | 8.59 | 13.7 | 7.33 | 2.16 | 1.52 | 0.871 | 0.885 | BLQ |
| Large intestine | 6.87 | 3.65 | 6.41 | 4.44 | 1.92 | BLQ | BLQ | ND | ND |
| Large intestine mucosa | NDd | 4.37 | 9.18 | 4.99 | 5.15 | ND | ND | ND | ND |
| Liver | 14.6 | 54.4 | 64.4 | 41.4 | 14.2 | 7.80 | 2.95 | 1.09 | BLQ |
| Lung(s) | 0.957 | 3.38 | 6.34 | 3.70 | 0.814 | BLQ | BLQ | ND | ND |
| Lymph node(s) | BLQ | 2.44 | 5.54 | 2.70 | ND | ND | ND | ND | ND |
| Lymph node(s), mandibular | BLQ | 2.87 | 5.33 | 2.73 | ND | ND | ND | ND | ND |
| Muscle | BLQ | 1.27 | 4.38 | 1.71 | BLQ | BLQ | ND | BLQ | ND |
| Myocardium | 1.92 | 5.77 | 10.7 | 4.41 | 1.47 | 1.36 | 0.901 | 0.777 | ND |
| Nasal mucosa | 1.87 | 3.04 | 6.38 | 4.03 | 0.931 | 0.834 | ND | ND | ND |
| Pancreas | 1.05 | 5.91 | 10.5 | 4.10 | BLQ | BLQ | BLQ | BLQ | ND |
| Pineal body | ND | 5.49 | 9.42 | 3.94 | ND | ND | ND | ND | ND |
| Pituitary gland | ND | 2.88 | 7.46 | 2.97 | ND | ND | ND | ND | ND |
| Preputial gland | 2.29c | 4.85c | 10.8c | 6.68c | 4.65c | 2.02 | 1.42 | ND | ND |
| Prostate gland | 0.998 | 4.33 | 13.9 | 3.66 | 0.839 | BLQ | BLQ | ND | ND |
| Rectum mucosa | 0.886 | 4.54 | 4.57 | 4.63 | BLQ | ND | ND | ND | ND |
| Salivary gland(s) | 1.40 | 4.52 | 9.15 | 3.36 | BLQ | BLQ | BLQ | ND | ND |
| Seminal vesicle(s) | BLQ | 1.92c | 2.89 | 1.64 | BLQ | BLQ | BLQ | ND | ND |
| Skin (nonpigmented) | 1.01 | 2.25 | 3.85 | 2.68 | BLQ | BLQ | BLQ | BLQ | ND |
| Small intestine | 4.59 | 12.1 | 18.9 | 11.3 | 2.38 | ND | ND | ND | ND |
| Small intestine mucosa | 7.89 | 32.5 | 39.6 | 26.9 | 13.6 | ND | ND | ND | ND |
| Spinal cord | BLQ | 2.68 | 5.84 | 1.76 | ND | ND | ND | ND | ND |
| Spleen | 1.40 | 3.50 | 6.76 | 3.17 | 1.09 | 0.830 | BLQ | BLQ | BLQ |
| Stomach | 1.58 | 3.61 | 7.41 | 3.93 | 1.14 | ND | ND | BLQ | ND |
| Stomach mucosa | ND | 7.38 | 14.0 | 4.65 | ND | ND | ND | ND | ND |
| Stomach wall | ND | 2.27 | 3.88 | 2.13 | ND | ND | ND | ND | ND |
| Testis(es) | 0.925 | 2.21 | 5.03 | 2.15 | 0.752 | BLQ | BLQ | BLQ | ND |
| Thymus | BLQ | 2.43 | 4.64 | 1.90 | BLQ | BLQ | BLQ | BLQ | ND |
| Thyroid | 2.09 | 5.74 | 10.6 | 4.05 | 3.23 | 2.20 | 2.78 | 1.56 | ND |
| Tongue | 1.15 | 4.04 | 8.00 | 3.10 | 0.809 | ND | ND | ND | ND |
| Tooth pulp | 1.23 | 2.79 | 4.30 | 3.48 | ND | ND | ND | ND | ND |
| Urinary bladder | 1.09 | 3.60 | NDd | 19.0 | ND | ND | ND | ND | ND |
| Urine | 9.28 | 21.5 | 148 | 67.9 | 24.0 | 1.58 | BLQ | ND | ND |
The last dose that these animals received was on day 21.
The actual collection time point was 73.4 h postdose, as the sample was collected approximately 88 min after the scheduled collection time (approximately 28 min outside of the acceptable standard range).
The tissue appeared to be fat soaked.
Not detectable due to flare from gastrointestinal contents (large intestine mucosa) or urine (urinary bladder).
[cyano-14C]isavuconazonium sulfate was administered at 30 mg/kg/day. Dose times are relative to the day 21 dose. BLQ, below the limit of quantitation (the lower limit of quantitation for day 21 was <0.748 μg eq [cyano-14C]isavuconazonium sulfate/g); ND, not detectable (the sample shape was not discernible from the background or surrounding tissue); QWBA, quantitative whole-body autoradiography.