Safety, tolerability and pharmacokinetics of an intravenous bolus of sildenafil in patients with pulmonary arterial hypertension

    loading  Checking for direct PDF access through Ovid


WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTPulmonary arterial hypertension (PAH) is a rare syndrome of dyspnoea and fatigue due to an increase in pulmonary vascular resistance. Although the disease remains incurable, targeted therapies have been shown to be beneficial to patients. Oral sildenafil (20 mg three times daily) is a phosphodiesterase type 5 inhibitor with proven efficacy on exercise capacity, symptoms and pulmonary haemodynamics in patients with PAH.WHAT THIS STUDY ADDSIt is advisable that chronic therapies for PAH, including oral sildenafil, not be interrupted. However, patients may not be able to take their medication because of an intervening illness or a requirement to undergo general anaesthesia, preventing oral drug administration. This study demonstrates that an intravenous bolus of 10 mg sildenafil in stable patients with PAH is safe, well tolerated and maintains plasma levels to preserve drug exposure.AIMSTo assess pharmacokinetics and pharmacodynamics of a 10 mg intravenous sildenafil bolus in pulmonary arterial hypertension (PAH) patients stabilized on 20 mg sildenafil orally three times daily.METHODSPharmacokinetic parameters were calculated using noncompartmental analysis.RESULTSAfter an acute increase, plasma concentrations stabilized within the range reported previously for a 20 mg oral tablet. At 0.5 h, mean ± SD changes from baseline were −8.4 ± 11.7 mmHg (systolic pressure), −2.6 ± 7.3 mmHg (diastolic pressure) and −3.5 ± 10.4 beats min−1 (heart rate). There was no symptomatic hypotension.CONCLUSIONSAlthough further research is warranted, a 10 mg sildenafil intravenous bolus appears to provide similar exposure, tolerability and safety to the 20 mg tablet.

    loading  Loading Related Articles