News - Part 35

Elderly

In healthy elderly volunteers, 65 years +, vardenafil’s half-life did not suffer a notable reduction from that or younger voulunteers (45 years and younger). There is a 52% higher AUC in the average elderly male than that of a younger male, that is within a clinical trials observed variability. Placebo monitored clinical trials produced no signs of an overall safety or effectiveness difference between older and younger volunteers.

Renal insufficiency

A control group of patients with an average renal function had comparable vardenafil pharmacokinetics to that of patients with severe (CLcr < 30 mL/min), moderate (CLcr 30 – 50 mL/min), or mild (CLcr 50 – 80 mL/min) renal impairment. Vardenafil plasma exposure and creatinine clearance (Cmax and AUC) depicted no apparent statistical correlation of significance. This data shows that renal function imparment is not grounds for dose adjustment.

Patients using dialysis should not use vardenafil, as the pharmacokinetics of vardenafil have yet to be observed in such a situation.

Hepatic Insufficiency

Canadian Vardenafil clearance, in patients with a mild to modest hepatic handicap (Child-Pugh A and B), was reduced in accordance.

Vardenafil Cmax and AUC were multiplied 1.2 times (Cmax by 22% and AUC by 17%) more than a healthy controlled subject after patients with a mild hepatic handicap took a 10mg dose. Adjusting dosage for mild hepatic impairments is not required. LEVITRA (vardenafil) Cmax multiplied 2.3 times (a 130% increase) and AUC multiplied 2.6 times (a 160% increase) more than a healthy controlled subject did after patients with a moderate hepatic handicap took a 10mg dose. Based on this a 5mg starting dose, which might eventually be upped to 10 or 20 mg, depending largely on efficacy and tolerability, should be utilized in patients with a moderate hepatic handicap. Individuals with a serious hepatic impairment (Child-Pugh C) should refrain from using vardenafil, as the pharmacokinetics of such a situation has yet to be researched.

Clinical Studies

In a few patients, a 20 mg dose of vardenafil produced an erection firm enough for sexual penetration (=60% rigidity) in only fifteen minutes during a placebo controlled Rigiscan study. 25 minutes after taking generic vardenafil, the statistical significance compared to placebo of the patients overall response became evident.

In every major efficacy trial, generic Vardenafil produced clinically substantial as well as statistically important improvement to erectile function compared to placebo, even including special population.

Vardenafil pills was issued to more than 3750 men battling with erectile dysfuction (ED) over the course of all trials. The men were aged between 18 and 89 years and a good number of them possessed multiple other medical conditions. More than 1630 patients took cheap vardenafil for at least 6 months.

The International Index of Erectile Function (IIEF) erectile function domain score captured that vardenafil 10 mg and 20 mg created clinically substantial as well as statistically important improvements compared to placebo in every major efficacy trial; this includes patients battling diabetes and post-prostatectomy patients. The percentage has improved with both patients rating their erections and the amount of patients who gain and maintain erections. (Tables 1 and 2).

Pharmacokinetics

Sep-22-2008

Pharmacokinetic girl

Absorption

After being applied orally, Vardenafil (Levitra) is quickly absorbed. 90% of patients reach Cmax, on an empty stomach, between 30 to 120 mins (median 1 hour) after oral dosing, but Cmax has been achieved as soon as 15 minutes in others.

Observed pharmacokinetic parameters have a substantial intra-subject and inter-subject variability caused by vardenafil’s ample first-pass metabolism. A 10mg dose of vardenafil has a mean absolute bioavailability of about 15%. Within the recommended dose range of 5mg-20mg of vardenafil, there almost a proportional increase of Cmax and AUC, after oral dosing.

Though the mean AUC went unaffected, the mean Cmax (rate of absorption) suffered an approximate 20% reduction and there was an approximate 60min delay in median tmax when vardenafil was taken with a high fat meal of approximately 57% fat. Pharmacokinetic parameters were not notably affected after consuming a ‘regular meal’ of approximately 30% fat. These results should prove that food is not required to take cheap vardenafil.

Distribution

Vardenafil’s mean steady state volume of distribution (Vss) is ~2.5 L/kg, referring to tissue distribution.

Plasma proteins are strongly bound to both vardenafil medication and it main circulating metabolite (M1) (~95% for M1 or parent drug). Total drug concentration is not dependent on this reversable protein binding. A maximum of only 0.0002% of a given dose of vardenafil is traceable in patient’s semen. This was taken from healthy subjects, an hour and a half post dosing.

Metabolism

Hepatic enzymes via CYP3A4 mostly metabolize vardenafil, but CYP3A5 and CYP2C9 isoforms make a few contributions. It takes about from 4 to 5 hours for the mean terminal elimination half-life from plasma.

The desethylation at the piperazine moiety of vardenafil produces human beings main circulating metabolite, M1, which may undergo further metabolism. The metabolite M1 has a terminal plasma elimination half-life of ~4 hours, equivalent to the parent drug. M1 appears in systemic circulation as it glucuronide-conjugated form (glucuronic acid). Non-glucuronidated M1 has a plasma concentration of only 26% of the parent compound. M1 has an efficacy contribution of about 7%, which means it has almost the same phosphodiesterase selectivity profile as vardenafil pills and an in vitro inhibitory potency for PDE5 of ~28%, in comparison to canadian vardenafil.

Excretion

Vardenafil drug has a 56 L/hour total body clearance, giving it a terminal half-life of between 4 and 5 hours. Generic Vardenafil is mostly excreted in the fecal matter (about 91 – 95% of given oral dose) and partially during urination (only about 2 – 6 % of given oral dose).

Effects

Sep-22-2008

Effects on Visual Perception

In one particular clinical trial, Visual fields, visual acuity, ERG latency, intraocular pressure, fundoscopic, nor slit lamp findings showed signs of being effected when visual functions were tested after a 40mg dose of vardenafil (two times the maximum recommended daily dosage). A minor group of patients spoke of color distortions in the blue/green and purple range, occurring one hour post dosing. After 6 hours the color distortions had been restored and did not return at 24 hours. There were no records of subjective visual symptoms on a majority of these patients. In separate trial, no association was made with dysfunction in intraocular pressure, visual acuity, or findings or slit lamp or fundoscopic examinations and once a day use of 10mg to 40mg doses of generic vardenafil over a 31 day period.

Effects on Blood Pressure

A slight, temporary drop in blood pressure has been attributed to taking vardenafil drug, but not, in most cases, to the extent of clinical concern. Supine systolic blood pressure had the maximum decrease, when being compared to placebo, of 6,9mmHg after 20 mg of vardenafil and 4.3 mmHg after 40 mg of vardenafil.

Effects on Cardiac Parameters

Volunteers, in fit physical condition, who swallowed a single dose of 80mg of cheap vardenafil (four times the maximum prescribed day to day dose) showed no effects on their ECGs of clinical relevance.

Effects on Exercise Performance in Patients with Coronary Artery Disease

The amount of treadmill exercise time compared to placebo, in a total of 39 males, between the ages of 48-77, with exercise induced ischaemia and coronary artery disease, were not altered in a placebo-controlled, two-period, cross-over trial after taking 10mg of vardenafil. The sum time of angina, compared to placebo, did not change. In the generic vardenafil group, the sum time of 1mm or more ST-segment depression was extended 15% in comparison to the placebo group (p<0.001). No patient was marked with any serious drug-related side effects during or after the trial.

Pharmacology

Sep-22-2008

The haemodynamic process of erecting a penis is grounded in the relaxation of smooth muscle in the corpus cavernosum and its allied arterioles. Nitric oxide (NO) is released from the corpus cavernosum’s nerve ends during sexual arousal. This triggers the enxyme guanylate cyclase causing the corpus cavernosum’s cyclic guanosine monophosphate (cGMP) levels to increase. This is what causes relaxation in the smooth muscle and allows freer blood flow into the penis, causing an erect penis. The rate of degradation via cGCP hydrolyzing phosphodiesterases (PDEs) and the rate of synthesis via the guanylate cyclase are the two factors that actually regulates the cGMP level. The cGMP specific phosphodiesterase type 5 (PDE5) is the main PDE in the corpus cavernosum of a human. Buy Levitra Plus

Canadian Vardenafil powerfully improves the effect of endogenous Nitric Oxide, which the corpus cavernosum unleashes during sexual arousal, by regulating PDE5. PDE5 is the enzyme that causes cGMP degradation in the corpus caverosum. The levels of cGMP are boosted in the corpus as a result of the PDE5 inhibition, causing smooth muscle relaxation and freer blood flow to the corpus cavernosum. This is how vardenafil creates the potential for men to respond naturally to sexual stimulation.

Quantitative analysis, outside of a living organism, display vardenafil as a selective inhibitor of PDE5. It has an IC50 of 0.7 nM for human platelet PDE5.

Vardenafils inhibitory effects are powerful on powerful on PDE5 than any other known phosphodiesterases (>1,000-fold more than PDE2, 3, 4, 7, 8, 9, and 10, >300-fold more than PDE11, >130-fold more than PDE1). In the isolated human corpus cavernosum, vardenafil drug causes a rise of cGMP causing muscle relaxation, as tested in vitro.

Cheap Vardenafil gives the conscious rabbit an erect penis, but it depends on endogenous nitric oxide synthesis and is potentiate by nitric oxide donors.

Name of the Drug

Vardenafil (CAS number: 224785-90-4) in the form of vardenafil hydrochloride trihydrate. The empirical formula of vardenafil hydrochloride trihydrate: C23H32N6O4S.HCI.3H2O. Molecular weight: 579.1 g/mol.

Description

Vardenafil hydrochloride trihydrate, a nearly colorness solid, is 2-[ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)-phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one hydrochloride trihydrate. Vardenafil hydrochloride trihydrate is soluble in 0.1M HCI and ethanol, freely soluble in methanol, and only slightly soluble in water and acetone.

LEVITRA comes in varying strength:

20 mg of vardenafil (23.705 mg of vardenafil hydrochloride trihydrate)
10 mg of vardenafil (11.852 mg of vardenafil hydrochloride trihydrate)
5 mg of vardenafil (5.926 mg of vardenafil hydrochloride trihydrate)

The above are drugs LEVITRA’S active ingredients, the tablets also contain: crospoyidone, colloidal anhydrous silica, microcrystalline cellulose, magnesium stearate, macrogol 400, titanium dioxide (CI77891), iron oxide red (CI77491), iron oxide yellow (CI77492).

Levitra Ingredients

Sep-20-2008

Levitra Ingredients

What it Looks Like

Levitra 5 mg tablets are orange film-coated round tablets with an embossed BAYER-cross on one side and “5” on the other side (sold in blister packs of 2 and 4).

Levitra 10 mg tablets are orange film-coated round tablets with an embossed BAYER-cross on one side and “10” on the other side (sold in blister packs of 2 and 4)

Levitra 20 mg tablets are orange film-coated round tablets with an embossed BAYER-cross on one side and “20” on the other side (sold in blister packs of 2 and 4)

Ingredients

Active Ingredients per tablet:

Levitra 5 – vardenafil (as hydrochloride trihydrate) 5 mg
Levitra 10 – vardenafil (as hydrochloride trihydrate) 10 mg
Levitra 20 – vardenafil (as hydrochloride trihydrate) 20 mg

Inactive Ingredients:

colloidal anhydrous silica
crospovidone
hypromellose
iron oxide red (CI 77491 – E172)
iron oxide yellow (CI 77492 – E172)
macrogol 400
magnesium stearate
microcrystalline cellulose
titanium dioxide (CI 77891 – E171)

Normal Dose Levitra

A doctor will determine the personal dosage for each individual patient based upon medical examination. Dosage comes in strength of 20 mg, 10 mg, and 5 mg.

Some men gain the capability to form an erection 15 mins after an oral dose of LEVITRA, but LEVITRA grug usually begins working after 25-60 mins. Sexual arousal, within 5 hours of taking a LEVITRA tablet should lead to an erect penis.

Other than eatting a fatty meal of 57% fat content or more and drinking alcohol, eating and drinking does not inhibit the effectiveness of Cheap LEVITRA. Normal eating habits can be observed prior to taking Canadian LEVITRA.

Avoid taking more than one dose of LEVITRA per day.

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