Pharmacokinetics of single dose sildenafil orally administered in canine models of chronic embolic pulmonary hypertension

Abstract

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.

Pulmonary hypertension in dog: Case report

“…1,2 However in veterinary medicine of small animals, treatment varies according to the clinical signs presented by patient. Normally are used diuretic drugs such as furosemide 11 , vasodilators 12 , phosphodiesterase inhibitors (pimobendan and sildenafil), 13,14 angiotensin-converting enzyme inhibitors (benazepril) 15 and calcium channels blokers (amlodipine besylate). 16 Oxygen therapy is also an important adjuvant in the treatment of pulmonary hypertension.…”

Efficacy of Beraprost Sodium Combined with Sildenafil and Its Effects on Vascular Endothelial Function and Inflammation in Patients Experiencing Left Heart Failure Complicated with Pulmonary Arterial Hypertension

“…Chronic left heart failure can alter both structure and function of the heart in patients to obviously weaken cardiac filling and ejection, resulting in congestion in the pulmonary circulation [ 2 ]. Once patients have left heart failure complicated with pulmonary arterial hypertension, treatment is not satisfactory because of the critical disease conditions, and if no prompt and effective measures are performed, respiratory failure will occur in the early stages [ 3 ]. Calcium channel blockers used to be administered to the patients with left heart failure and pulmonary arterial hypertension to dilate blood vessels and reduce pulmonary arterial pressure, but the efficacy needs to be improved [ 4 ].…”