TABLE 1.
Concentrations of radioactivity in tissues and fluids determined by QWBA at specified times after single oral-dose administration of [cyano-14C]isavuconazonium sulfate in male pigmented ratsc
| Matrix | Concn of [cyano-14C]isavuconazonium sulfate (μg eq/g) at: |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| 1 h | 2 h | 4 h | 8 h | 24 h | 72 h | 144 h | 336 h | 672 h | |
| Adrenal cortex | 5.76a | 11.0a | 7.14 | 7.91 | 2.46 | 1.03 | 0.348 | 0.169 | BLQa |
| Adrenal gland(s) | 5.05a | 10.6a | 6.99 | 7.50 | 2.31 | 0.908 | 0.270 | 0.136 | BLQa |
| Adrenal medulla | 2.58a | 4.44a | 5.05 | 4.01 | 1.32 | 0.317 | 0.085 | 0.047 | BLQa |
| Aorta | 0.640 | 1.14 | 0.339 | 0.427 | ND | ND | ND | ND | ND |
| Arterial wall | 0.645 | 0.923 | 0.348 | 0.465 | ND | ND | ND | ND | ND |
| Bile | 147 | 66.6 | 21.6 | 19.0 | ND | ND | ND | ND | ND |
| Blood | 0.463 | 0.603 | 0.252 | 0.247 | 0.092 | BLQ | ND | ND | ND |
| Bone | 0.048 | 0.070 | BLQ | BLQ | BLQ | ND | ND | ND | ND |
| Bone marrow | 0.717 | 0.822 | 0.287 | 0.279 | 0.054 | ND | ND | ND | ND |
| Brain cerebellum | 0.597 | 0.887 | 0.234 | 0.322 | BLQ | ND | ND | ND | ND |
| Brain cerebrum | 0.533 | 0.808 | 0.216 | 0.272 | BLQ | ND | ND | ND | ND |
| Brain medulla | 0.641 | 0.912 | 0.249 | 0.321 | BLQ | ND | ND | ND | ND |
| Brain olfactory lobe | 0.485 | 0.591 | 0.189 | 0.234 | BLQ | ND | ND | ND | ND |
| Bulbourethral gland | 0.846 | 1.54 | 0.543 | 0.534 | 0.094 | ND | ND | ND | ND |
| Cecum | 1.47 | 0.725 | 0.696 | 0.625 | 0.448 | ND | ND | ND | ND |
| Cecum mucosa | 1.33 | 1.01 | 1.01 | 0.916 | 0.512 | ND | ND | ND | ND |
| Diaphragm | 0.879 | 1.25 | 0.385 | 0.501 | 0.079 | ND | ND | ND | ND |
| Epididymis | 0.556 | 1.42a | 0.754 | 0.577 | 0.116 | BLQ | ND | ND | ND |
| Esophagus | 0.721 | 0.974 | 0.346 | 0.382 | 0.081 | BLQ | ND | ND | ND |
| Exorbital lacrimal gland | 1.35 | 1.94 | 0.675 | 0.698 | 0.106 | BLQ | ND | ND | ND |
| Eye lens | BLQ | 0.050 | BLQ | 0.077 | 0.060 | ND | ND | ND | ND |
| Eye uveal tract | 1.02 | 1.59 | 1.04 | 1.15 | 0.374 | 0.097 | ND | ND | ND |
| Eye(s) | 0.180 | 0.312 | 0.200 | 0.191 | 0.084 | BLQ | ND | ND | ND |
| Fat (brown) | 1.27 | 3.76 | 1.35 | 1.26 | 0.142 | BLQ | ND | ND | ND |
| Fat (mesenteric) | 0.784 | 2.34 | 2.68 | 3.24 | 0.287 | BLQ | ND | ND | ND |
| Fat (reproductive) | 0.557 | 1.84 | 2.11 | 2.79 | 0.747 | BLQ | ND | ND | ND |
| Fat (white) | 1.04 | 2.47 | 2.50 | 2.84 | 0.275 | BLQ | ND | ND | ND |
| Harderian gland | 1.66 | 3.74 | 1.13 | 1.11 | 0.165 | ND | ND | ND | ND |
| Intra-orbital lacrimal gland | 1.27 | 1.91 | 0.675 | 0.675 | 0.129 | ND | ND | ND | ND |
| Kidney cortex | 2.04 | 2.77 | 1.14 | 1.12 | 0.176 | BLQ | ND | ND | ND |
| Kidney medulla | 2.40 | 3.29 | 1.21 | 0.998 | 0.159 | BLQ | ND | ND | ND |
| Kidney(s) | 2.29 | 3.04 | 1.19 | 1.06 | 0.170 | BLQ | ND | ND | ND |
| Large intestine | 0.789 | 1.05 | 0.402 | 0.650 | 0.206 | BLQ | ND | ND | ND |
| Large intestine mucosa | 0.879 | 1.11 | 0.470 | 0.781 | 0.312 | BLQ | ND | ND | ND |
| Liver | 24.7 | 15.7 | 6.21 | 5.31 | 1.45 | 0.392 | 0.138 | BLQ | ND |
| Lung(s) | 0.743 | 0.915 | 0.292 | 0.381 | 0.082 | BLQ | ND | ND | ND |
| Lymph node(s) | 0.529 | 0.651 | 0.289 | 0.300 | 0.054 | ND | ND | ND | ND |
| Lymph node(s), mandibular | 0.577 | 0.730 | 0.263 | 0.317 | 0.048 | ND | ND | ND | ND |
| Muscle | 0.530 | 0.812 | 0.255 | 0.278 | BLQ | BLQ | ND | ND | ND |
| Myocardium | 1.03 | 1.47 | 0.489 | 0.589 | 0.080 | BLQ | ND | ND | ND |
| Nasal mucosa | 0.589 | 1.38 | 0.467 | 0.436 | 0.124 | 0.042 | ND | ND | ND |
| Pancreas | 1.49 | 1.60 | 0.676 | 0.769 | 0.080 | BLQ | ND | ND | ND |
| Pineal body | NR | 1.13 | 0.345 | 0.490 | ND | ND | ND | ND | ND |
| Pituitary gland | 0.811 | 1.25 | 0.431 | 0.535 | 0.084 | ND | ND | ND | ND |
| Preputial gland | 0.576a | 1.47a | 0.900a | 1.28a | 0.202a | 0.073 | ND | ND | ND |
| Prostate gland | 0.975 | 1.71 | 0.608 | 0.572 | 0.069 | BLQ | ND | ND | ND |
| Rectum mucosa | 0.581 | 1.04 | 0.207 | 0.513 | 0.221 | BLQ | ND | ND | ND |
| Salivary gland(s) | 1.12 | 1.52 | 0.485 | 0.531 | 0.070 | ND | ND | ND | ND |
| Seminal vesicle(s) | 0.157 | 0.341 | 0.194 | 0.163 | 0.059 | BLQ | ND | ND | ND |
| Skin (nonpigmented) | 0.378 | 0.872 | 0.325 | 0.321 | 0.080 | BLQ | ND | ND | ND |
| Skin (pigmented) | 0.520 | 0.910 | 0.511 | 0.461 | 0.121 | 0.052 | ND | ND | ND |
| Small intestine | 1.50 | 1.72 | 1.07 | 0.970 | 0.259 | ND | ND | ND | ND |
| Small intestine mucosa | 2.52 | 2.18 | 1.78 | 1.45 | 0.553 | ND | ND | ND | ND |
| Spinal cord | 0.595 | 0.948 | 0.284 | 0.315 | BLQ | ND | ND | ND | ND |
| Spleen | 0.763 | 0.850 | 0.306 | 0.380 | 0.093 | BLQ | ND | ND | ND |
| Stomach | 1.21 | 1.77 | 0.540 | 0.513 | 0.093 | 0.077 | ND | ND | ND |
| Stomach mucosa | 2.22 | 2.43 | 0.891 | 0.614 | 0.104 | 0.103 | ND | ND | ND |
| Stomach wall | 0.946 | 1.01 | 0.356 | 0.362 | 0.086 | BLQ | ND | ND | ND |
| Testis(es) | 0.507 | 1.03 | 0.520 | 0.512 | 0.146 | 0.070 | ND | ND | ND |
| Thymus | 0.543 | 0.827 | 0.259 | 0.287 | 0.072 | ND | ND | ND | ND |
| Thyroid | 0.858 | 1.09 | 0.389 | 0.447 | 0.104 | ND | ND | ND | ND |
| Tongue | 0.954 | 1.17 | 0.428 | 0.422 | 0.049 | ND | ND | ND | ND |
| Tooth pulp | 0.592 | 0.628 | 0.261 | 0.216 | 0.048 | ND | ND | ND | ND |
| Urinary bladder | NDb | 1.63a | 0.535 | 0.406 | ND | ND | ND | ND | ND |
| Urine | 17.5 | 54.7 | 8.61 | 8.95 | 2.90 | 0.195 | ND | ND | ND |
a
The tissue appeared to be fat soaked.
b
The urinary bladder could not be sampled due to the flare from the urine.
c
[cyano-14C]isavuconazonium sulfate was administered at 5 mg/kg. The correction factor of 1.1352 (sulfate/free form) was applied to calculate the concentrations of free base equivalents of radioactivity in tissues, bile, blood, and urine. BLQ, below the limit of quantitation (<0.0414 μg equivalents [cyano-14C]isavuconazonium sulfate/g); ND, not detectable (the borders of the sample were indiscernible from the background or surrounding tissue); NR, not represented (tissue was not present in the section); QWBA, quantitative whole-body autoradiography.