Document Type : Original Article


1 Department of Analytical Chemistry, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey

2 Department of Toxicology, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey

3 Department of Pharmacology, Faculty of Pharmacy, Atatürk University, Erzurum, Turkey


Erectile dysfunction (ED) diseases have almost affected 100 million men all over the world. Orally administered phosphodiesterase 5 (PDE 5) inhibitors are the most used pharmaceutical formulations for the treatment of ED. In this study, it is aimed to investigate the metabolomics feature of orally administered vardenafil in rats. To carry out the experimental procedure eight male Wistar albino rats were used. Their livers were gently removed and metabolomics profiles of each sample were determined by UPLC Q-TOF MS. Identification of metabolites was achieved by the METLIN database. Cluster analysis was also performed via Principle Component Analysis. Several metabolites were identified and results were evaluated by XCMS software. UPLC Q-TOF MS could be successfully applied to profile biomarkers and help us understand the molecular mechanisms of vardenafil usage. It was concluded that the level of some metabolites, responsible for the collagen synthesis and Kreb’s cycle, has been statistically significant after the vardenafil administration.



    1. Hellstrom WJG, Gittelman M, Karlin G, et al. Vardenafil for treatment of men with erectile dysfunction: Efficacy and safety in a randomized, double‐blind, placebo‐controlled trial. J Androl 2002;23(6):763-771.
    2. Fugl-Meyer AR, Lodnert G, Bränholm IB, et al. On life satisfaction in male erectile dysfunction. Int J Imot Res 1997;9(3):141-148.
    3. Chew KK, Earle CM, Stuckey BG, et al. Erectile dysfunction in general medicine practice: Prevalence and clinical correlates. Int J Impot Res 2000;12(1):41-45.
    4. Thoma C. Erectile dysfunction: Vardenafil in men with T2DM. Nat Rev Urol 2016;13(3):126. doi: 10.1038/nrurol.2016.30.
    5. Montorsi F, Hellstrom WJG, Valiquette L, et al. Vardenafil provides reliable efficacy over time in men with erectile dysfunction. Urology 2004; 64(6):1187-1195.
    6. Setter SM, Iltz JL, Fincham JE, et al. Phosphodiesterase 5 inhibitors for erectile dysfunction. Ann Pharmacother 2005;39(7-8):1286-1295.
    7. Alonso A, Marsal S, Julià A. Analytical methods in untargeted metabolomics: State of the art in 2015. Front Bioeng Biotechnol 2015; Doi:10.3389/fbioe. 2015.00023.
    8. Radovits T, Bömicke T, Kökény G, et al. The phosphodiesterase-5 inhibitor vardenafil improves cardiovascular dysfunction in experimental diabetes mellitus. BrJ Pharmacol 2009;156(6):909-919.
    9. Wu Q, Zhang H, Dong X et al. UPLC-Q-TOF/MS based metabolomic profiling of serum and urine of hyperlipidemic rats induced by high fat diet. J Pharm Anal 2014;4(6):360-367.
    10. Veselkov KA, Vingara LK, Masson P, et al. Optimized preprocessing of ultra-performance liquid chromate-graphy/mass spectrometry urinary metabolic profiles for improved information recovery. Anal Chem 2011;83(15):5864-5872.
    11. Wang J, Li Z, Chen J, et al. Metabolomic identification of diagnostic plasma biomarkers in humans with chronic heart failure. Mol Biosyst 2013;9(11):2618-2626.
    12. Kretovich WL, Kariakina TI, Kazakova OV, et al. Biosynthesis of amino acids from sucrose and Krebs cycle metabolites by Rhizobium lupini bacteroids. Mol Cell Biochem 1983;51(1):61-66.
    13. Tapiero H, Mathé G, Couvreur P, et al. II. Glutamine and glutamate. Biomed Pharmacother 2002;56(9):446-457.
    14. Fenves AZ, Kirkpatrick HM, Patel VV, et al. Increased anion gap metabolic acidosis as a result of 5-oxoproline (pyroglutamic acid): A role for acetaminophen. Clin J Am Soc Nephrol 2006;1(3):441-447.