Pharmacokinetics of single dose sildenafil orally administered in canine models of chronic embolic pulmonary hypertension
| Autor: | Ryota Akabane, Naoyuki Takemura, Hiroyuki Tazaki, Atsushi Sakatani, Mizuki Ogawa, Yuichi Miyagawa, Hirosumi Miyakawa, Masayoshi Nagakawa, Touko Sato |
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| Rok vydání: | 2020 |
| Předmět: |
Drug doses
040301 veterinary sciences Sildenafil Hypertension Pulmonary sildenafil Administration Oral Pharmacology Sildenafil Citrate Microsphere 0403 veterinary science 03 medical and health sciences Power model chemistry.chemical_compound Dogs Pharmacokinetics pulmonary hypertension medicine Animals Dog Diseases 030304 developmental biology 0303 health sciences Full Paper General Veterinary business.industry Area under the curve 04 agricultural and veterinary sciences medicine.disease Pulmonary hypertension Microspheres Disease Models Animal chemistry Area Under Curve dog microsphere Female business pharmacokinetics Canine model |
| Zdroj: | The Journal of Veterinary Medical Science |
| ISSN: | 1347-7439 0916-7250 |
| Popis: | Information regarding the pharmacokinetics of oral sildenafil in dogs with pulmonary hypertension is limited. In this study, we examined the pharmacokinetics of oral sildenafil in a canine model of chronic embolic pulmonary hypertension (CEPH). The CEPH model was developed by repeatedly injecting microspheres into the pulmonary arteries. The pharmacokinetics of oral sildenafil at 1, 2 and 4 mg/kg was evaluated using four dogs with pulmonary hypertension in the fasted state. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil was well tolerated in this study. Proportional increments in the maximum plasma concentration and area under the curve extrapolated to infinity at drug doses of 1, 2 and 4 mg/kg were detected using a power model analysis. No significant differences were observed among the three doses in the time to maximum plasma concentration. The mean residence time and elimination half-life were slightly but significantly higher at a dose of 4 mg/kg than at a dose of 1 mg/kg. |
| Databáze: | OpenAIRE |
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