Indications
Avanafil is primarily indicated for the treatment of erectile dysfunction. This therapeutic option is designed to improve erectile function and is suitable for administration prior to anticipated sexual activity.
Pharmacodynamics
Avanafil functions as a potent and competitive inhibitor of phosphodiesterase type 5 (PDE5), with a significant in vitro inhibitory concentration (IC50) of 5.2 nM. Its selective mechanism of action results in considerably reduced activity against PDE6 and other PDE enzymes, rendering it less prone to induce visual disturbances and cardiovascular side effects compared to less selective PDE5 inhibitors like sildenafil and vardenafil. Avanafil is notable for its rapid onset of action, enabling it to be taken as soon as 15 minutes before sexual intercourse. It is important to be cautious of potential drug interactions, particularly when avanafil is used concomitantly with certain antihypertensive medications, such as alpha blockers, or with substantial amounts of alcohol. Moreover, there is an associated risk of developing non-arteritic anterior ischemic optic neuropathy (NAION) with PDE5 inhibitors, a condition characterized by sudden vision loss, which necessitates immediate discontinuation of the drug and medical consultation. In some regions, a history of NAION or other degenerative retinal conditions may contraindicate the use of avanafil.
Absorption
Avanafil is rapidly absorbed after oral administration, with peak plasma concentrations typically reached within 30 to 45 minutes. The oral bioavailability of avanafil appears to be low to moderate, though precise studies have not been formalized. When taken with food, there is an observed delay in the time to reach peak plasma concentration (Tmax) by approximately 1.12 to 1.25 hours, along with a 39% reduction in peak plasma concentration (Cmax); however, the overall exposure (AUC) remains only slightly affected.
Metabolism
Avanafil undergoes extensive metabolism predominantly via the cytochrome P450 isoenzyme CYP3A4 and, to a lesser extent, CYP2C9. Two principal metabolites, M4 and M16, are formed and present in plasma at 23% and 29% of the parent drug's concentration, respectively. The M16 metabolite does not exhibit pharmacological activity, whereas the M4 metabolite retains an inhibitory capacity for PDE5 at 18% of avanafil's potency, contributing to approximately 4% of the drug's pharmacological effects.
Mechanism of Action
Avanafil functions by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which is specifically responsible for breaking down cyclic guanosine monophosphate (cGMP) in the corpus cavernosum surrounding the penis. Upon sexual arousal, nitric oxide is released locally, activating the enzyme guanylate cyclase. This activation leads to the production of cGMP, which facilitates the relaxation of smooth muscles and enhances blood flow to the penis, resulting in an erection. It is important to note that PDE5 inhibitors, such as avanafil, depend on the natural release of nitric oxide to be effective, and therefore, they do not produce any effects in the absence of sexual arousal.
