LIFANED Film-coated tablet Ref.[115341] Active ingredients: Sildenafil

Absorption

Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 – 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is approximately 40% (range 25 – 63%). The oral pharmacokinetics of sildenafil is proportional over the recommended dose range (25 – 100 mg). When sildenafil is taken with a high fat meal, the rate of absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in C_max of 29%.

Distribution

The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues. Sildenafil and its major circulating N-desmethyl metabolite are both approximately 96% bound to plasma proteins. Protein binding is independent of total drug concentrations. In healthy volunteers receiving sildenafil (100 mg single dose), less than 0,0002% (average 188 ng) of the administered dose was present in ejaculate 90 minutes after dosing.

Biotransformation

Sildenafil is cleared predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil. This metabolite has a PDE selectivity profile similar to sildenafil and an in vitro potency for PDE5 approximately 50% that of the parent compound. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half-life of approximately 4 hours.

Elimination

The total body clearance of sildenafil is 41 L/h with a resultant terminal phase half-life of 3 – 5 hours. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).

Special populations

Elderly

Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, with free plasma concentrations approximately 40% greater than those seen in healthy younger volunteers (18 – 45 years).

Renal insufficiency

In volunteers with mild (creatinine clearance (CLcr) = 50 – 80 mL/min) to moderate (CLcr = 30 – 49 mL/min) renal impairment, the pharmacokinetics of a single oral dose of sildenafil (50 mg) were not altered. In volunteers with severe (CLcr ≤ 30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in mean increases in AUC (100%) and C_max (88%) compared to age-matched volunteers with no renal impairment.

Hepatic insufficiency

In volunteers with hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was reduced, resulting in increases in AUC (84%) and C_max (47%) compared to age-matched volunteers with no hepatic impairment.