Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: Effect of feeding and dose proportionality
| Autor: | Ryota Akabane, Atsushi Sakatani, Naoyuki Takemura, Yuichi Miyagawa, Hiroyuki Tazaki, Touko Sato |
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| Rok vydání: | 2018 |
| Předmět: |
040301 veterinary sciences
Sildenafil Vasodilator Agents Cmax Administration Oral 030204 cardiovascular system & hematology Pharmacology Sildenafil Citrate 0403 veterinary science Food-Drug Interactions 03 medical and health sciences Power model chemistry.chemical_compound Dogs 0302 clinical medicine Dose proportionality Pharmacokinetics Animals Cross-Over Studies Dose-Response Relationship Drug General Veterinary Chemistry Area under the curve 04 agricultural and veterinary sciences Crossover study respiratory tract diseases Plasma concentration cardiovascular system |
| Zdroj: | Journal of Veterinary Pharmacology and Therapeutics. 41:457-462 |
| ISSN: | 0140-7783 |
| DOI: | 10.1111/jvp.12487 |
| Popis: | Basic information related to the pharmacokinetics of sildenafil in dogs is scarce. This study aimed to describe the pharmacokinetic properties of oral sildenafil and determine the effect of feeding and dose proportionality. The effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated using a crossover study with six dogs. In addition, the dose proportionality of sildenafil ranging 1-4 mg/kg was evaluated using five dogs in the fasted states. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil administrations were well tolerated in all studies. Feeding reduced the area under the curve extrapolated to infinity (AUCinf ) and the maximum plasma concentration (Cmax ) significantly. The elimination half-life (T1/2 ) did not differ between the fasted and the fed states. For dose proportionality, nonproportional increases in AUCinf and Cmax at 1-4 mg/kg doses were detected by a power model analysis. |
| Databáze: | OpenAIRE |
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