Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension

摘要

AIMS To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). METHODS Sixteen patients with PH (aged 29-85 years), received one single oral dose of vardenafil (5, 10 or 20mg). The haemodynamic effect was assessed over a 60min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60min using liquid chromatography-tandem mass spectrometry. RESULTS At 60min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P<0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P=0.015) and 12.1% (range -24.0 to 94.4; P=0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P<0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P=0.002; n=14) in the PVR/systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r=-0.579, P=0.019) and between vardenafil concentrations and change in PVR (r=-0.662, P=0.005). CONCLUSIONS Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.