In healthy subjects, tadalafil exposure (AUC) increased dose-proportionally over the dose range of 2.5 to 20 mg. Steady-state plasma concentrations are achieved within 5 days after once-daily dosing, and exposures are approximately 1.6-fold greater than those after a single dose. Mean tadalafil concentrations measured in an independent study in healthy male subjects after administration of a single oral dose of 20 mg and single and multiple daily doses of 5 mg.
· Absorb
Following a single oral dose, the maximum plasma concentration (Cmax) of tadalafil is achieved in 30 minutes to 6 hours (median, 2 hours). The absolute bioavailability of tadalafil following oral administration has not been determined.
The rate and extent of tadalafil absorption are not affected by food; therefore Cialis can be taken with food or alone.
· Distribute
The mean apparent volume of distribution after oral administration was approximately 63 L, indicating distribution of tadalafil into tissues. At therapeutic concentrations, 94% of tadalafil in plasma is protein bound.
Less than 0.0005% of the dose occurs in the semen of healthy subjects.
· Metabolism
Tadalafil is primarily metabolized by CYP3A4 to its catechol metabolite. Catechol metabolites undergo extensive methylation and glucuronidation to form methylcatechol and methylcatechol glucuronidate conjugates, respectively. The major circulating metabolite is methylcatechol glucuronide. Methylcatechol concentration is less than 10% of the glucuronide concentration.
In vitro data indicate that the metabolite is not expected to be pharmacologically active at the concentrations of the metabolite observed.
· Excretion
In healthy subjects, the mean oral clearance of tadalafil is 2.5 L/hr and the mean terminal half-life is 17.5 hours. Tadalafil is primarily excreted as a metabolite, primarily in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
· Geriatrics
Healthy male elderly subjects (65 years or older) had lower oral clearance of tadalafil, resulting in an exposure (AUC) 25% higher than in healthy subjects 19 to 45 years of age, without an effect on Cmax. There is no need to adjust dosage based solely on age. However, older adults should be considered more sensitive to the drug [see Use in Specific Populations].
· Diabetics
In diabetic men, a 10 mg dose of tadalafil resulted in an approximately 19% reduction in exposure (AUC) and a 5% reduction in Cmax compared to healthy subjects. No dosage adjustment is required.
· Patients with prostatic hyperplasia
No statistical differences in exposure (AUC and Cmax) were observed between older (70 to 85 years) and younger (≤60 years) subjects in patients with BPH after single and multiple doses of 20 mg of tadalafil Significant differences in learning. No dosage adjustment is required.
