A Comparative Pharmacokinetic and Pharmacodynamic Study of Sildenafil in Adult Smokers and Non Smokers.

Abstract

Sildenafil citrate is an orally given PDE-5 inhibitor that has been shown to be an effective treatment for male erectile dysfunction (ED). It is mostly metabolised via the cytochrome P450 hepatic isoenzymes 3A4 (one major pathway) and 2C9 (another significant pathway) (a minor route)

Long-term smoking was found to have an inhibitory effect on CYP3A4 in a preclinical investigation, indicating that CYP3A4 is likely to be suppressed to some extent in smokers. which may influence the clearance and plasma concentrations of sildenafil, a CYP3A4 substrate medication.

Cannabis, a frequently abused drug, used as smoking is known to block the CYP3A4 pathway, which is the most common route for sildenafil metabolism. Changes in the pharmacokinetics of sildenafil in cigarette and/or cannabis users could have a negative impact on the drug's safety profile.

The goal of this study was to see how cannabis and/or cigarette smoking affected sildenafil pharmacokinetics, pharmacodynamics, safety, and tolerability, as well as to evaluate total antioxidant capacity and malondialdehyde levels as oxidative stress markers in smokers.

The subjects were recruited at random and then assigned according to their smoking behaviours in this randomised open-label parallel trial. A total of 36 subjects (n = 36) were separated into three groups: Nonsmokers were in Group 1 (n = 12), cigarette smokers were in Group 2 (n = 12), and cannabis smokers were in Group 3 (n = 12).

Cigarette smokers' sildenafil exposure (AUC0–t) increased by 61 percent (p 0.05) as compared to non-smokers, while cannabis users' AUC0–t increased by