Eazialis 5
Pharmacodynamic properties:
Eazialis® is a potent, selective, reversible inhibitor of cyclic guanosine
monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). When sexual
stimulation causes the local release of nitric oxide, inhibition of PDE5 by
Eazialis® produces increased levels of cGMP in the corpus cavernosum. This
results in smooth muscle relaxation and inflow of blood into the penile tissues,
thereby producing an erection. Tadalafil has no effect in the absence of sexual
stimulation. Eazialis® administered to healthy subjects produced no significant
difference compared to placebo in supine systolic and diastolic blood pressure, or
in standing systolic and diastolic blood pressure, and no significant change in
heart rate. There were no clinically relevant effects on sperm concentration, sperm
count, motility or morphology after daily doses of 10 mg and 20 mg for 6
months.
Pharmacokinetic properties:
- Tadalafil is readily absorbed after oral administration and the mean maximum
observed plasma concentration (Cmax) is achieved at a median time of 2 hours
after dosing.
- The rate and extent of absorption of tadalafil are not influenced by food, thus
Eazialis® may be taken with or without food. The time of dosing (morning versus
evening) had no clinically relevant effects on the rate and extent of absorption.
- The mean volume of distribution is approximately 63 liters, indicating that
tadalafil is distributed into tissues. At therapeutic concentrations, 94% of Tadalafil
in plasma is bound to proteins. Protein binding is not affected by impaired renal
function.
- Less than 0.0005% of the administered dose appeared in the semen of healthy
subjects.
- Tadalafil is predominantly metabolized by the cytochrome P450 (CYP3A4)
isoform.
- The mean oral clearance for tadalafil is 2.5 L/hr and the mean half-life is 17.5
hours in healthy subjects.
- Tadalafil is excreted predominantly as inactive metabolites, mainly in the faeces
(approximately 61% of the dose) and to a lesser extent in the urine (approximately
36% of the dose).