Pharmacokinetics of single‐dose sildenafil administered orally in clinically healthy dogs: Effect of feeding and dose proportionality |
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| Authors: | R Akabane T Sato A Sakatani Y Miyagawa H Tazaki N Takemura |
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| Institution: | 1. Laboratory of Veterinary Internal Medicine II, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino‐shi, Japan;2. Laboratory of Biomolecular Chemistry, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino‐shi, Japan |
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| Abstract: | 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. |
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| Keywords: | dog dose proportionality feeding pharmacokinetics sildenafil |
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