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Practical gUidElinEs For tHE trEatmEnt oF ErEctilE dysFUnction and PEyroniE´s disEasE

Table 28.2. Pharmacokinetic properties of sildenafil, tadalafil, and vardenafil

 

Parameter

Sildenafil (100 mg)

Tadalafil (20 mg)

Vardenafil (20 mg)

Cmax

560 mg/l

378 mg/l

18.7 mg/l

Tmax

0.8–1 h

2 h

0.9 h

T1/2

2.6–3.7 h

17.5 h

3.9 h

aUc

1685 mg/h/l

8066 mg/h/l

56.8 mg/h/l

Protein binding

96%

94%

94%

Bioavailability

41%

na

15%

data based on fasted state, higher recommended dose, and information from the European medicine Evaluation association statements on product characteristics.

Cmax maximal concentration, Tmax time to maximum plasma concentration, T1/2 plasma elimination half-time, AUC area under curve – serum concentration time curve.

source: (reprinted from Wespes et al. 6. copyright 2006, with permission from Elsevier).

Figure 28.4. schematic illustration of the pathways involved in regulation of signals mediated by adenosine and guanosine cyclic monophosphates (camP and cgmP) in the urogenital tract (reprinted from Uckert et al. 21. copyright 2006, with permission from Elsevier).

Various transmitters

CNP

 

 

 

out

 

 

NO

 

 

 

membrane

 

 

 

in

 

 

 

PKA

ATP

GTP

 

 

 

Other

 

 

GTP

 

 

 

regulatory

cAMP

 

 

proteins

 

PKG I

Ion channels

 

 

 

cGMP

 

 

 

Other

 

 

 

PDE 1

 

 

regulatory

PDE 4

PDE 2

 

proteins

 

 

PDE 7

 

 

Ion channels

PDE 8

 

PDE 1

 

PDE 10

 

 

 

PDE 5

 

PDE 11

PDE 3

 

PDE 9

 

 

 

 

 

PDE 10

5’AMP

PDE 11

5’GMP

 

is injected into the corpora cavernosa.24,25 By increasing cyclic AMP levels, it causes smooth muscle relaxation. In spite of high efficacy, alprostadil has a low tolerability due to uncommon adverse events such as penile pain and priapism and,chronically,penile fibrosis or curvature (Grade A – level Ia).

Papaverine hydrochloride alone or in combination with phentolamine or a combination of papaverine, phentolamine, and alprostadil (triple mix) is highly effective and has found frequent use in daily practice; however, it is not approved as standard therapy. Generally, intracavernous injections are contraindicated in patients with sickle cell anemia and with other conditions that predispose to priapism.

Intraurethral Therapy Intraurethral alprostadil therapy is less invasive than intracavernous injections therapies. It offers moderate efficacy and tolerability in the management of general ED. Adverse events resemble intracavernous therapy; in addition, systemic side effects have been observed (Grade A – level Ib).26

Vacuum Constriction Devices

Vacuum constriction devices (VCD) are widely available and beneficial for patients who disapprove of medical therapy or those who have any contraindication. Vacuum devices work by creating negative pressure to the pendulous