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High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

To evaluate the pharmacokinetic parameters of a single oral dose of vardenafil in patients with pulmonary hypertension (PH).

Methods

Sixteen patients with PH received vardenafil in single oral doses (20, 10 or 5 mg), and repeated blood sampling for up to 9 h was performed. Vardenafil plasma concentration was determined using liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using model-independent analysis.

Results

The plasma vardenafil concentration increased rapidly and exhibited a median time to maximum plasma concentration (tmax) of 1 h and a mean elimination half-life (t1/2) of 3.4 h. The geometric mean and standard deviation of (1) the peak plasma concentration (Cmax) was 21.4 ± 1.7 μg/L, (2) the normalized Cmax (Cmax, norm) 79.1 ± 1.6 g/L, (3) the area under the time–concentration curve (AUC) 71.5 ± 1.6 μg · h/L and (4) the normalized AUC (AUCnorm) 261.6 ± 1.7 g · h/L. Patients co-medicated with bosentan reached tmax later and had a 90% reduction of Cmax, Cmax, norm, AUC and AUCnorm.

Conclusion

The pharmacokinetic profile of vardenafil overall revealed considerable inter-individual variability in patients with PH. Co-medication with bosentan resulted in a pharmacokinetic drug interaction, leading to significantly decreased plasma concentrations of vardenafil. Therapeutic drug monitoring for individual dose optimization may be warranted.

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Acknowledgments

The authors are grateful to Lisa Wernroth (Uppsala Clinical Research Center, Uppsala, Sweden) for help with the statistical analyses and Cecilia Jakobsson for help with monitoring of the study.

Financial support statement

This study was not supported by external funding.

Disclosures

Dr Wikström has received lecture fees from Actelion Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline and Pfizer. The other authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Division of Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umeå University and Umeå University Hospital, 901 85, Umeå, Sweden

    A. M. Sandqvist & J. Schneede

  2. Department of Medical Sciences, Uppsala University and Uppsala University Hospital, Uppsala, Sweden

    D. Henrohn, H. C. Egeröd & B. G. Wikström

  3. Department of Chemistry, National Veterinary Institute (SVA), Uppsala, Sweden

    M. Hedeland & U. G. Bondesson

  4. Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden

    M. Hedeland & U. G. Bondesson

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  1. A. M. Sandqvist
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Correspondence to A. M. Sandqvist.

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Sandqvist, A.M., Henrohn, D., Schneede, J. et al. High inter-individual variability of vardenafil pharmacokinetics in patients with pulmonary hypertension. Eur J Clin Pharmacol 69, 197–207 (2013). https://doi.org/10.1007/s00228-012-1323-5

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  • DOI: https://doi.org/10.1007/s00228-012-1323-5

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