THE PHARMACOKINETICS OF 1954U89, 1, 3-DIAMINO-7-(1-ETHYLPROPYL)-8-METHYL-7H-PYRROLO-(3, 2-f )QUINAZOLINE, IN DOGS AND RATS AFTER INTRAVENOUS AND ORAL ADMINISTRATION
✍ Scribed by S. D. STUDENBERG; J. L. WOOLLEY; D. V. DEANGELIS; W. A. WARGIN
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 122 KB
- Volume
- 18
- Category
- Article
- ISSN
- 0142-2782
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✦ Synopsis
1954U89, 1, 3-diamino-7-(1-ethylpropyl)-8-methyl-7H-pyrrolo-(3, 2-f )quinazoline, is a potent, lipid-soluble inhibitor of dihydrofolate reductase. The pharmacokinetics and bioavailability of 1954U89 were examined in male beagle dogs and male CD rats. Dogs received single intravenous (2´5 mg kg 71 ) and oral (5´0 mg kg 71 ) doses of 1954U89 with and without successive administration of calcium leucovorin. Single intravenous (5´0 mg kg 71 ) and oral (10 mg kg 71 ) doses of [1,3-14 C 2 ]1954U89 were administered to rats. Plasma concentrations of total radiocarbon were determined by scintillation counting, and intact 1954U89 was measured by HPLC. The mean plasma half-life was 3´2+0´62 and 4´2+0´68 h after intravenous and oral administration, respectively, to dogs. The pooled plasma half-life after intravenous administration to rats averaged 1´2 h; a reliable plasma half-life value after oral administration could not be determined. Mean total-body clearance was 2´4+0´39 and 4´5+1´1 L h 71 kg 71 after intravenous and oral administration, respectively, to dogs, and averaged 12 and 77 L h 71 kg 71 after intravenous and oral administration, respectively, to rats. Neither clearance nor bioavailability of 1954U89 in dogs was aected signi®cantly by administration of calcium leucovorin. Absolute bioavailability was 54+12% in dogs and 16% in rats.