Impulse, Eight Times Impulse
IMPULSE is rapidly absorbed after oral administration. Cmax is reached as early as 15 minutes (median 60 minutes) of oral dosing in the fasted state.
Due to a considerable first-pass effect, the mean absolute oral bioavailability is about 15%.
After oral dosing of IMPULSE AUC and Cmax increase almost dose-proportionally over the recommended dose range(60-120 mg).
When IMPULSE is taken with a high fat meal (containing 57%fat), the rate of absorption is reduced with an increase in the median Tmax of 60 minutes and a mean reduction in Cmax of 20%. IMPULSE AUC was not affected. After a normal meal (containing 30% fat) IMPULSE pharmacokinetic parameter(Cmax, Tmax, and AUC) were not affected at all.
Based on these results IMPULSE can be taken with of without food.
Description: The mean steady state volume of distribution (Vss) for IMPULSE is 208 L, indicating distribution into the tissues.
IMUPULSE and its major circulating metabolite (M1) are highly bound to plasma proteins (about 95% for parent frug or M1). This protein binding is reversible and independent of total drug concentrations.
Based upon measurements of IMPULSE in semen of healthy subjects 90 minutes after dosing, not more than 0.00012% of the administered dose may appear in the semen of patients.
Metabolism:
IMPULSE is metabolized predominantly by hepatic enzymes via CYP3A4, with some contribution from CYP2A5 and CYP2C9 isoforms.
Mean elimination half life (t1/2) is about 4-5 hours.
In humans, the major circulating metabolite (M1) results from desethylation at the piperazine moiety of IMPULSE, and is subject to further metabolism. The plasma elimination half life of the metabolite M1 is approximately 4 h, comparable to the parent drug.
Parts of M1 are in form of its glucuronide-conjugate (glucuonic acid) in systemic circulation.
The plasma concentration of non-glucuronidated M1 is about 26% that of the parent compound. The metabolite M1 show a phosphodiesterase Selectivity Profile Similar to that of IMPULSE and an in vitro inhibitory potency for PDE5 of approximately 28% compared to IMPULSE, resulting in an efficacy contribution of about 7%.
Excretion:
The total boby clearance of IMPULSE is 56 l/h with a resultant terminal half life of about 4-5 hours.
After oral administration, IMPULSE is excreted as metabolites predominantly in the faeces (approximately 91-95% of administered oral dose) and to a lesser extent in the urine (approximately 2-6% of administered oral dose).
Pharmacokinetics in special populations:
Elderly:
IMPULSE hepatic clearance in healthy elderly volunteers (60 years or over) was reduced as compared to volunteers of younger age (45 years and below). On average, elderly males had a 52% higher AUC than younger males which is within the variability observed in clinical trials. No overall differences in safety or effectiveness were observed between elderly and younger subjects in placebo controlled clinical trials.
Renal insufficiency:
In patients with mild (Clcr>50-80 ml/min) to moderate (CLcr>30-50 ml/min) renal impairment, IMPULSE pharmacokinetics were similar to that of a normal renal function control group. In volunteers with severe renal impairment (CLcr

120mg*7 grain