International Journal of
Medicine and Medical Sciences

  • Abbreviation: Int. J. Med. Med. Sci.
  • Language: English
  • ISSN: 2006-9723
  • DOI: 10.5897/IJMMS
  • Start Year: 2009
  • Published Articles: 531

Review

Pharmacokinetic drug interactions of phosphodiesterase-5 inhibitors mediated by cytochrome P450 3A4 isoform

Srinivas Pentyala
  • Srinivas Pentyala
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.Departments of Urology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Aleef Rahman
  • Aleef Rahman
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Supriya Mishra
  • Supriya Mishra
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Sowmya Muthiki
  • Sowmya Muthiki
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Emily Hughes
  • Emily Hughes
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Abhishek Bikkani
  • Abhishek Bikkani
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Kathleen Cervo
  • Kathleen Cervo
  • Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Christopher Maruso
  • Christopher Maruso
  • Departments of Urology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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Sardar Khan
  • Sardar Khan
  • Departments of Urology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
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  •  Accepted: 09 November 2010
  •  Published: 01 February 2011

Abstract

 

Novel drugs for Erectile Dysfunction (ED) must be assessed for their interactions with other already approved medications that are processed through similar metabolic pathways. The cytochrome P450 enzyme family, in particular 3A4 isoform, is ubiquitously used to oxidize azole antifungals, erythromycin, and HIV protease inhibitors. Administering multiple medications using cytochrome P450 CYP3A4 (3A4) as a primary metabolic route may cause unexpected toxicological effects in patients. Current U.S Food and Drug Administration (FDA) approved ED drugs such as sildenafil (Viagra), tadalafil (Levitra), and vardenafil (Cialis), all Phosphodiesterase-5 inhibitors, are also metabolized by 3A4. The overlapping metabolic pathways for the above mentioned PDE-5 inhibitors are known, however it is still imperative to discover any negative clinical manifestations that may arise from their concomitant use or their use with other substrates that are metabolized by 3A4 enzyme. Worldwide, approximately 150 million men are struggling with ED, making this research a valid obligation. Consequently, interaction of the widely prescribed ED drugs and their interactions with 3A4 enzyme are discussed in this review.

 

Key words: Cytochrome P450, 3A4, erectile dysfunction, Viagra, Cialis, Levitra.