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Vardenafil.

Jay M Young
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Abstract

Vardenafil hydrochloride is a potent and highly selective inhibitor of phosphodiesterase Type 5 that increases blood flow to the penis during sexual stimulation and helps restore the ability to achieve and sustain an erection in men with erectile dysfunction. Vardenafil was developed specifically to be an effective and safe oral medication for the treatment of erectile dysfunction, with potential advances over existing therapies. This review summarises key findings during the rapid and aggressive development of this compound, from in vitro assays to Phase III trials with both broad and special populations. Emphasis is placed on the presentation of data that demonstrates the clinical effectiveness and safety of this agent which is anticipated to be available in 2003.

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3',5'-Cyclic-GMP PhosphodiesterasesAnimalsClinical Trials as TopicCyclic Nucleotide Phosphodiesterases, Type 5Erectile DysfunctionHumansImidazolesMalePhosphodiesterase InhibitorsPhosphoric Diester HydrolasesPiperazinesSulfonesTriazinesVardenafil DihydrochlorideJournal ArticleReview

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Jay M Young. 2002. Vardenafil.. https://doi.org/10.1517/13543784.11.10.1487

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3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Intravenous sildenafil is a potent pulmonary vasodilator in children with congenital heart disease.

BACKGROUND: Increased pulmonary vascular resistance (PVR) because of congenital heart disease (CHD) may be caused by a dysfunction in endogenous pulmonary endothelial nitric oxide (NO) production. In other forms of pulmonary vascular disease with increased PVR, an elevated activity of a phosphodiesterase type 5 (PDE-5), responsible for the degradation of cyclic guanidine monophosphate (cGMP), the second messenger of endothelially produced NO, has been demonstrated. This study compares the effects of inhaled NO before and after the specific inhibition of the PDE-5 by intravenous sildenafil (Viagra) in pre- and postoperative children with increased PVR because of CHD. METHODS AND RESULTS: 12 children with congenital heart disease (age 0.2 to 15.7 years, median 2.4 years) and increased mean pulmonary arterial pressure, and 12 postoperative children (age 0.11 to 0.65 years, median 0.32 years) with increased PVR (8.3+/-1.0 Wood Units*m2) were studied during cardiac catheterization ("cath laboratory"), or within 2 hours after return from cardiac surgery ("post op"), respectively. All were sedated, tracheally intubated and paralyzed. During alveolar hyperoxygenation (FiO2=0.65), the effects of inhaled NO (20 ppm) were compared before and after the stepwise infusion of sildenafil ("cath laboratory", 1 mg/kg; post op, 0.25 mg/kg). Intravenous sildenafil more effectively reduced PVR than NO (11.5% versus 4.3% in the "cath laboratory" patient group, P<0.05, and 25.8% versus 14.6% in the post op patient group, P=0.09. The increase in cGMP in response to NO was potentiated (2- to 2.4-fold) by PDE-5 inhibition. While the vasodilating effects of sildenafil showed pulmonary selectivity, its infusion was associated with increased intrapulmonary shunting in the postoperative patients (Qs/Qt=16.5+/-4.7% to 25.5+/-18.2% P=0.04). CONCLUSIONS: Intravenous sildenafil is as effective as inhaled NO as a pulmonary vasodilator in children with congenital heart disease. Although clinically insignificant in this study, increased intrapulmonary shunting with sildenafil may be disadvantageous in some patients after CHD surgery.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Structure of the catalytic domain of human phosphodiesterase 5 with bound drug molecules.

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3',5'-Cyclic-GMP Phosphodiesterases↗