Pharmacokinetic parameters of FIN and metabolites I andIV in dogs after single 10 and 80 mg/kg oral doses of [14C]FIN
| Dose (mg/kg) and Parameter | Total Radioactivity1-a | AFR1-b | FIN | MetaboliteI | Metabolite IV | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| 10 | 80 | 10 | 80 | 10 | 80 | 10 | 80 | 10 | 80 | |
| C max(μg/ml) | 3.4 | 12.5 | 0.11 | 0.36 | 2.1 | 7.4 | 1.3 | 4.2 | ND1-c | 0.09 |
| t max (hr) | 1.5 | 4, 301-d | 5.5 | 4, 301-d | 1.5 | 4, 301-d | 6.3 | 7, 301-d | ND | 4, 301-d |
| AUC0-∞(μg · hr/ml) | 66.3 | 474.5 | 2.7 | 12.4 | 25.4 | 215.4 | 32.8 | 199.8 | ND | 3.7 |
| AUC (% change) | — | 616 | — | 439 | — | 748 | — | 509 | ||
| % of total14C1-e | 3.5 | 2.6 | 38.5 | 45.4 | 49.5 | 42.1 | 0.80 | |||
Results are average values from the same two dogs given both doses.
↵1-a Total radioactivity (TotalRAD; undifferentiated) is expressed as μg FIN-eq/ml.
↵1-b Defined as that fraction of radioactivity not retained on a solid-phase extraction cartridge (cyano Sep-Pak).
↵1-c ND, not determined. Individual plasma samples of dogs at the low dose were not analyzed for metabolite IV; however, analysis of a pooled plasma sample showed that the monocarboxylic acid metabolite IV accounted for 0.8% of the total 14C in plasma.
↵1-d Due to the prolonged absorption of the high dose in one dog, both tmax values are shown.
↵1-e Estimated by use of the following expression: (AUC/AUCTotal RAD) · 100.