Pharmacokinetic dynamic relationships
Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension
Article first published online: 13 NOV 2012
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 74, Issue 6, pages 990–998, December 2012
How to Cite
Henrohn, D., Sandqvist, A., Hedeland, M., Egeröd, H., Bondesson, U. and Wikström, G. (2012), Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension. British Journal of Clinical Pharmacology, 74: 990–998. doi: 10.1111/j.1365-2125.2012.04303.x
- Issue published online: 13 NOV 2012
- Article first published online: 13 NOV 2012
- Accepted manuscript online: 20 APR 2012 05:05AM EST
- Received; 26 August 2011; Accepted; 13 April 2012; Accepted Article Published Online; 20 April 2012
- phosphodiesterase inhibitor;
- pulmonary hypertension;
- right heart catheterization;
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Phosphodiesterase-5 (PDE5) inhibitor therapy is effective in the treatment of patients with pulmonary hypertension (PH). All available PDE5 inhibitors, sildenafil, tadalafil and vardenafil have been reported to cause pulmonary vasodilation acutely in patients with PH. There is a lack of information on the haemodynamic effects in relation to plasma concentrations for the available PDE5 inhibitors and the drug concentration to obtain optimal clinical effect is unknown.
WHAT THIS STUDY ADDS
• This study provides information on the correlation between vardenafil plasma drug concentration and the acute changes in haemodynamics in patients with PH after a single oral dose of vardenafil.
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 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography–tandem mass spectrometry.
RESULTS At 60 min 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.