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

Authors

  • Dan Henrohn,

    Corresponding author
    1. Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala
      Dr Dan Henrohn MD MSc Pharm, Department of Medical Sciences, Uppsala University, Uppsala University Hospital, SE-751 85, Uppsala, Sweden. Tel.: +46 18 611 9361, Fax: +46 18 525 618, E-mail: dan_henrohn@hotmail.com
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  • Anna Sandqvist,

    1. Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå University Hospital, Umeå
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  • Mikael Hedeland,

    1. Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala
    2. Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
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  • Hanna Egeröd,

    1. Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala
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  • Ulf Bondesson,

    1. Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala
    2. Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
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  • Gerhard Wikström

    1. Department of Medical Sciences, Uppsala University, Uppsala University Hospital, Uppsala
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Dr Dan Henrohn MD MSc Pharm, Department of Medical Sciences, Uppsala University, Uppsala University Hospital, SE-751 85, Uppsala, Sweden. Tel.: +46 18 611 9361, Fax: +46 18 525 618, E-mail: dan_henrohn@hotmail.com

Abstract

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.

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