ISSN 2756-3855
International Journal of Urology and Nephrology ISSN 2091-1254 Vol. 6 (8), pp. 001-010, August, 2018. © International Scholars Journals
Review
Pharmacokinetic drug interactions of phosphodiesterase-5 inhibitors mediated by cytochrome P450 3A4 isoform
Srinivas Pentyala1,2,*, Aleef Rahman1, Supriya Mishra1, Sowmya Muthiki1, Emily Hughes1, Abhishek Bikkani1, Kathleen Cervo1, Christopher Maruso2 and Sardar Khan2
1Departments of Anesthesiology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York
2Departments of Urology, School of Medicine, Stony Brook University Medical Center, Stony Brook, New York.
Accepted 06 April, 2018
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.