Overview of Metabolism Process of Sildenafil

Sildenafil is primarily metabolized in the liver. The active ingredient in Viagra, sildenafil is rapidly absorbed when administered orally, with maximum plasma concentration achieved within 1 hour. Its metabolism is primarily facilitated by the hepatic microsomal isoenzymes.

Role of Hepatic Metabolism in Sildenafil Breakdown

Hepatic metabolism plays a significant role in the metabolism of sildenafil. Sildenafil is cleared almost exclusively by hepatic metabolism. This process involves the breaking down of sildenafil by the liver into various metabolites.

Role of Cytochrome P450 3A4 in Sildenafil Metabolism

Cytochrome P450 3A4 (CYP3A4) is the major route for the metabolism of sildenafil.This isoenzyme converts sildenafil into an active metabolite, facilitating its clearance from the body.

The majority of sildenafil metabolism is driven by CYP3A4.

Lesser Role of CYP2C9 Hepatic Isoenzymes in Sildenafil Metabolism

CYP2C9 hepatic isoenzymes also play a role in the metabolism of sildenafil, albeit a minor one compared to CYP3A4. This secondary pathway contributes to the clearance of sildenafil but to a lesser extent.

Formation of Active Metabolite with Properties Similar to Sildenafil

The metabolism of sildenafil results in the formation of an active metabolite, N-desmethyl sildenafil. This metabolite is similar in structure and function to the parent compound, sildenafil, and has a similar PDE-5 inhibition profile.

Elimination Process of Sildenafil

After sildenafil is metabolized, it's then eliminated from the body. The elimination of sildenafil is facilitated by its transformation into metabolites, which are excreted predominantly in the feces and to a lesser extent, in the urine.

Sildenafil Plasma Elimination Half-Life (4 hours)

The half-life of sildenafil in plasma is approximately 4 hours. This means that after around 4 hours, half of the sildenafil dosage administered is cleared from the bloodstream. Some men may still achieve a satisfactory erection after 10 hours, as traces of the drug remain, but the duration will become shorter. After 24 hours, all traces of the drug in the bloodstream have practically vanished.

The Concept of Absolute Bioavailability and Its Relation to Sildenafil (41%)

The absolute bioavailability of sildenafil is approximately 41%. This refers to the fraction of sildenafil that reaches the systemic circulation intact after administration.

Impact of First-Pass Metabolism on Sildenafil

First-pass metabolism significantly impacts the bioavailability of sildenafil. After oral administration, sildenafil undergoes rapid and extensive first-pass metabolism in the liver before it reaches the systemic circulation.

Pharmacokinetics of Radiolabelled [14C]-Sildenafil

Studies using radiolabelled [14C]-sildenafil help understand the drug's pharmacokinetics, showing its rapid absorption, metabolism, and elimination pathways.

Rapid Absorption and Fecal Elimination of Sildenafil

After oral administration, sildenafil is rapidly absorbed. It is then excreted as metabolites predominantly in the feces, accounting for about 80% of the administered dose.

Role of Urine in Sildenafil Excretion

In addition to fecal excretion, around 13% of the administered sildenafil dose is excreted in the urine. This contributes to the overall elimination of the drug from the body.

N-desmethylation of Sildenafil and Its Major Circulating Metabolite

N-desmethylation of sildenafil forms the major circulating metabolite. This process involves the removal of a methyl group from sildenafil, transforming it into its major active metabolite.

Phosphodiesterase PDE Affinity of the Metabolite (40% of Sildenafil)

The major metabolite resulting from the N-desmethylation of sildenafil has a phosphodiesterase PDE affinity that is about 40% of that of sildenafil. This implies that the metabolite retains some of the PDE-5 inhibitory activity that is characteristic of sildenafil.