1990 Volume 5 Issue 1 Pages 111-119
Plasma levels of KW-3049 were determined after single oral and/or intravenous administration to male and female rats, dogs and monkeys.
1. When KW-3049 was administered to male rats intravenously at the doses of 30, 100 and 300μg/kg, the plasma levels of KW-3049 declined bi-exponentially with the half-lives of 36.4, 29.8 and 28.2 min, at the terminal elimination phase, respectively.
2. When KW-3049 was administered to female rats intravenously at the doses of 100μg/kg, the plasma levels of KW-3049 were similar to those of male rats and declined bi-exponentially with the half-life of 30.1 min at the terminal elimination phase.
3. After oral administration of KW-3049 to male rats at the doses of 1, 3 and 10mg/kg, the plasma levels reached the maximum of 2.4±0.3, 19.5±6.2 and 103.1±41.3ng/ml at 0.25 ?? 0.5hr, respectively, and declined exponentially with the respective half-lives of 2.1, 2.8 and 4.2 hr. Bioavailability of each dose was 4.3, 6.8 and 25.6%, respectively.
4. After oral administration of KW-3049 to female rats at the doses of 1, 3 and 10mg/kg, the plasma levels reached the maximum of 5.7±3.2, 64.7± 49. 371.7±187.8ng/ml at 0.25 ?? 0.5hr, respectively, and declined exponentially with the respective half-lives of 1.7, 2.3 and 4.1 hr. Bioavailability of each dose was 11.0, 23.5 and 95.9%, respectively.
5. When KW-3049 was administered to male beagle dogs intravenously at the doses of 3, 10 and 30μg/kg, the plasma levels of KW-3049 declined bi-exponentially with the half-lives of 69.1, 81.3 and 259.8min, at the terminal elimination phase, respectively.
6. After oral administration of KW-3049 to male beagle dogs at the doses of 0.5, 1.0 and 1.5mg/kg, the plasma levels reached the maximum of 1.6±0.8, 9.8±1.5 and 25.9±5.1 ng/ml at 0.5 ?? 4hr, respectively, and declined exponentially with the respective half-lives of 1.6±0.5, 3.1±2.1 and 4.0±1.3hr. Bioavailability of each dose was 2.5±1.2, 8.3±3.7 and 17.9±3.5%, respectively.
7. After oral administration of KW-3049 to male monkeys at a dose of 1 mg/kg, the plasma levels reached the maximum of 21.3±23.0 ng/ml at 0.7±0.3 hr and declined exponentially with the respective half-life of 4.7±1.2 hr.
