Disposition of [3H]fluvastatin following single oral doses in beagle dogs and rhesus monkeys with bile fistulae
| Autor: | Francis L. S. Tse, Jeremy G. Dain, Gaetana Kalafsky |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
medicine.medical_specialty Biliary Fistula Indoles Cmax Pharmaceutical Science Administration Oral Urine Absorption (skin) Pharmacology Biology Beagle Fatty Acids Monounsaturated Dogs Species Specificity Oral administration Internal medicine medicine Animals Pharmacology (medical) Fluvastatin Anticholesteremic Agents Fissipedia General Medicine biology.organism_classification Macaca mulatta Endocrinology Excretory system Hydroxymethylglutaryl-CoA Reductase Inhibitors medicine.drug |
| Zdroj: | Biopharmaceuticsdrug disposition. 16(3) |
| ISSN: | 0142-2782 |
| Popis: | The disposition of [3H]fluvastatin was examined following single oral doses in dogs (12.4 mg kg-1) and monkeys (0.48 and 45.5 mg kg-1) with bile fistulae. Serial plasma and complete urine, feces, and bile were collected at designated intervals for 3 or 4 d, and were analyzed for total radioactivity and unchanged fluvastatin. In the dog, peak radioactivity concentrations (Cmax) averaged 7260 ng equiv. mL-1 and the mean time to peak (tmax) was approximately 9 h. In the monkey, the mean radioactivity tmax values were approximately 5 and 13 h following the low and high doses, the respective Cmax values being 116 and 10,400 ng equiv. mL-1. The mean AUC of total radioactivity was proportional to the dose while that of fluvastatin was overproportional to dose, suggesting dose independent absorption but saturable first-pass effect. The AUC ratio of unchanged fluvastatin versus total radioactivity was approximately 63% in the dog, and 9% and 13% for the low and high doses, respectively in the monkey. The bile was the major excretory route of radioactivity (dog, 56%; low-dose monkey, 73%; high-dose monkey, 69%) whereas the renal pathway accounted for < 5% of the dose in both species. Approximately 12% of the biliary radioactivity in the dog was due to intact fluvastatin, compared with 0% and 7.5% after the low and high doses in the monkey. These results showed a smaller extent of fluvastatin metabolism in the dog than in the monkey, and suggested that metabolism in the monkey was saturable in the dose range studied. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text