Cumulative excretion and retention of radioactivity after single intravenous and oral doses of 14C-DB289 to rats and cynomolgus monkeys
Results are expressed as mean percentage radioactive dose.
Rat | Monkey | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Biological Sample (Collection Time) | Intravenous (1 mg/kg) | Oral (10 mg/kg) | Oral (50 mg/kg) | Intravenous (1 mg/kg) | Oral (5 mg/kg) | |||||||||||||
| Male | Female | Male | Female | Male | Female | Male | Female | Male | Female | |||||||||
| Urine | ||||||||||||||||||
| 0-24 h | 4.4 | 3.5 | 3.0 | 4.3 | 2.2 | 3.0 | 6.1 | 7.1 | 1.1 | 1.0 | ||||||||
| 0-168 h | 5.7 | 4.8 | 4.0 | 5.4 | 2.8 | 3.8 | 8.4 | 10.2 | 2.0 | 1.9 | ||||||||
| Feces | ||||||||||||||||||
| 0-24 h | 28.8 | 18.7 | 50.1 | 37.1 | 59.2 | 48.9 | 5.6 | 2.6 | 30.1 | 12.5 | ||||||||
| 0-168 h | 55.2 | 36.0 | 72.5 | 66.2 | 79.5 | 70.4 | 24.6 | 23.1 | 70.2 | 69.5 | ||||||||
| Total excretion a (0-168 h) | 60.9 | 40.8 | 76.5 | 71.6 | 82.3 | 74.2 | 33.0 | 33.3 | 72.2 | 71.4 | ||||||||
| Liver (168 h) | 22.4 | 41.4 | 12.9 | 21.3 | 5.6 | 16.3 | 40.0b | 41.9b | 11.1b | 11.4b | ||||||||
| GIT (168 h) | 2.0 | 1.6 | 1.7 | 1.6 | 0.9 | 0.9 | N.M. | N.M. | N.M. | N.M. | ||||||||
| Carcass (168 h) | 8.4 | 8.9 | 8.6 | 7.7 | 4.2 | 5.0 | N.M. | N.M. | N.M. | N.M. | ||||||||
| Total retention (168 h) | 32.8 | 51.9 | 23.2 | 30.6 | 10.7 | 22.2 | 41.2 c | 42.9 c | 11.5 c | 11.7 c | ||||||||
|
Total recovery (168 h)
|
93.7
|
92.7
|
99.5
|
102.2
|
93.0
|
96.4
|
74.2
|
76.2
|
83.7
|
83.1
| ||||||||
GIT, gastrointestinal tract; N.M., not measured.
↵ a Total excretion results for urine include cage washings for both rat and monkey, and results for feces include cage debris (mainly uneaten food contaminated with excreta) for monkeys only.
↵ b Forty-three days postdose (monkeys only).
↵ c Total retention at 43 days postdose in monkeys includes the kidneys, heart, lungs, and GIT wall (which totaled 1.0-1.3% of dose after intravenous administration and 0.3-0.4% of dose after oral administration), but not the remaining carcass (which was not measured).