Inhibition by canine liver microsome activities by FDA-approved and nonapproved veterinary pharmaceutical agents
Compound by Therapeutic Area or Mechanism of Action | Canine P450 Implicated | Inhibition (3 μM) | IC50a |
|---|---|---|---|
| % | μM | ||
| Anesthetic | |||
| Propofol | 2B11 | 40.8 | 15.9 ± 8.3 |
| Antiemetic | |||
| Metoclopramide HCl | 2D15 | 24.8 | 36.3 ± 18.3 |
| Ondansetron HCl | 1A1/2 | 37.8 | 2.4 ± 1.1 |
| 2D15 | 42.3 | 1.9 ± 0.3 | |
| Antidiarrheal | |||
| Loperamide | 2B11 | 49.7 | 1.5 ± 0.3 |
| 2C21/41 | Activation (+25.4%) | ||
| 2D15 | 86.1 | 0.0072 ± 0.0022 | |
| 3A12/26 | 54.0 | 32.3 ± 17.0 | |
| Antifungal | |||
| Griseofulvin | 2B11 | 14.6 | |
| Ketoconazole | 1A1/2 | 27.4 | 588 ± 370 |
| 2B11 | 48.3 | 5.2 ± 1.0 | |
| 2C21/41 | 25.0 | 12.6 ± 4.2 | |
| 2D15 | 81.7 | 0.47 ± 0.09 | |
| 3A12/26 | 87.9 | 0.72 ± 0.21 | |
| Miconazole nitrate (control) | 1A1/2 | 52.4 | 2.4 ± 0.4 |
| (cocktail) | 45 | 2.9 ± 0.2 | |
| 2B11 | 84 | 0.0099 ± 0.0009 | |
| 2C21/41 | 66.7 | 1.3 ± 0.8 | |
| (cocktail) | 70 | 1.5 ± 0.3 | |
| 2D15 | 94.0 | 0.036 ± 0.008 | |
| (cocktail) | 85 | 0.066 ± 0.007 | |
| 3A12/26 | 80.0 | 0.54 ± 0.11 | |
| (cocktail) | 88 | 0.54 ± 0.11 | |
| Antimicrobial | |||
| Amoxicillin | 2C21/41 | 10.4 | |
| Cefpodoxime proxetil | <10 | ||
| Cephalexin hydrate | <10 | ||
| Chloramphenicol | 2B11 | 22.4 | |
| Doxycycline hyclate | <10 | ||
| Enrofloxacin | <10 | ||
| Erythromycin | <10 | ||
| Metronidazole | <10 | ||
| Sulfadimethoxine | 2B11 | 17.2 | |
| Sulfasalazine | <10 | ||
| Trimethoprim | 2D15 | 17.2 | |
| Antineoplastic | |||
| Cyclophosphamide | <10 | ||
| Doxorubicin | 2D15 | 10.8 | |
| Vincristine | 1A1/2 | 11.7 | |
| 2C21/41 | 28.8 | 19.4 ± 6.1 | |
| 2D15 | 24.7 | 8.6 ± 0.6 | |
| 3A12/26 | 15.5 | ||
| Antiparasitic | |||
| Ivermectin | 1A1/2 | 10.6 | |
| 2B11 | 15.8 | ||
| 2C21/41 | 22.0 | ||
| 2D15 | 18.4 | ||
| 3A12/26 | 14.8 | ||
| Praziquantel | 2C21/41 | 15.2 | |
| Anxiolytic/sedative/anticonvulsant | |||
| Buspirone | <10 | ||
| Clomipramine HCl | 2D15 | 84.0 | 0.10 ± 0.05 |
| Diazepam | 2B11 | 33.9 | 9.4 ± 4.2 |
| Fluoxetine HCl | 2B11 | 29.4 | 10.1 ± 1.0 |
| 2D15 | 53.8 | 3.3 ± 3.9 | |
| Phenobarbital | <10 | ||
| Diuretic | |||
| Furosemide | <10 | ||
| Endocrine replacement | |||
| l-Thyroxine | 2B11 | 13.0 | |
| 2C21/41 | 16.4 | ||
| 2D15 | 10.7 | ||
| H1 antagonist | |||
| Diphenhydramine | 2D15 | 18.6 | |
| H2 antagonist | |||
| Cimetidine | <10 | ||
| Famotidine | <10 | ||
| Ranitidine HCl | 2C21/41 | 11.1 | |
| % | μM | ||
| Immunosuppressant | |||
| Cyclosporin A | 2B11 | 10.4 | |
| 3A12/26 | 36.2 | 14.1 ± 23.2 | |
| Nonsteroidal anti-inflammatory drug | |||
| Carprofen | <10 | ||
| Deracoxib | 2B11 | 16.0 | |
| Etodolac | <10 | ||
| Ketoprofen | <10 | ||
| Meloxicam | <10 | ||
| Piroxicam | 2B11 | 17.5 | |
| 2C21/41 | 15.9 | ||
| Proton pump inhibitor | |||
| Omeprazole | 1A1/2 | 32.4 | 41.4 ± 13.3 |
| 2D15 | 13.0 | ||
| Respiratory | |||
| Theophylline | <10 | ||
| Steroid | |||
| Prednisolone | 2D15 | 13.6 | |
| Prednisolone, methyl- | <10 | ||
| Prednisone | 1A1/2 | 12.3 | |
| 2C21/41 | 18.2 | ||
| 2D15 | 17.4 | ||
| Proprietary compounds | |||
| 1 | 1A1/2 | 12.0 | |
| 2B11 | 28.7 | 27.4 ± 11.1 | |
| 2 | 2B11 | 19.0 | |
| 2D15 | 92.2 | 0.11 ± 0.02 | |
| 3 | 2D15 | 77.0 | 0.96 ± 0.60 |
| 3A12/26 | 18.1 | 23.9 ± 5.4 | |
| 4 | 2D15 | 69.0 | 1.5 ± 0.6 |
| 3A12/26 | 34.7 | 4.2 ± 1.4 | |
| 5 | 2D15 | 9.6 | 50.1 ± 13.5 |
| 6 | 2C21/41 | 3.8 | 224 ± 274 |
| 2D15 | 14.9 | 42.7 ± 40.8 | |
| 7 | 2D15 | 23.0 | 15.4 ± 8.9 |
| 8 | 2D15 | 39.7 | 3.5 ± 0.5 |
|
| 3A12/26 | 23.9 | 10.1 ± 1.2 |
↵ a A nine-point IC50 value was generally determined when the single-point IC50 screen demonstrated >25% inhibition