Vardenafil is a new PDE5 inhibitor launched for oral treatment of male erectile
dysfunction and it has significant structural similarity with sildenafil (Viagra?), which
was the first PDE5 inhibitor introduced in 1998 for this indication. Vardenafil is
synthesized in three steps starting with a cyclization reaction of 2-ethyoxybenzamidine
with 2-butyramidopropionic acid and ethoxyallyl chloride to construct the imidazotriazine
ring system, followed by sulfonation to the corresponding sulfonyl chloride and
subsequent condensation with 1-ethylpiperazine. The potency of PDE5 inhibition by
vardenafil (IC50=0.7 nM) is ～10 times greater than that of sildenafil (IC50=6.6 nM).
Vardenafil is typically administered in single doses of 10 and 20 mg. The time to reach
maximum plasma concentration is 0.75 h, which is slightly shorter than those of sildenafil
(tmax=1.16 h) and tadalafil (tmax=2h), and the half-life is 4–5 h. Although it is almost
completely absorbed following oral administration, the mean absolute bioavailability of a
10 mg dose is ～15%, resulting from extensive first pass metabolism. Vardenafil is
metabolized in the liver primarily by CYP3A4 and is eliminated mainly in feces. In
clinical studies, 10–20 mg doses of vardenafil was well tolerated and efficacious in
patients with ED of various severities, including subjects with comorbidities such as
diabetes mellitus or hypertension or hyperlipidemia. The side-effect profile of vardenafil
is similar to that of sildenafil, with headache, flushing, dyspepsia and nasal congestion
being the most common adverse events. Vardenafil has systemic vasodilatory properties,
which can cause transient decrease in supine blood pressure; however, it does not appear
to translate into clinical effects. The mean maximum decreases in supine systolic blood
pressure following 20 and 40 mg vardenafil were 6.9 and 4.3 mmHg, respectively, when compared to placebo. However, single and multiple oral doses of vardenafil up to 40 mg
produced no clinically relevant changes in the ECGs of normal male volunteers.
erectil dysfunction;PDE5 inhibitor
Vardenafil Hydrochloride Trihydrate (cas# 330808-88-3) has therapeutic applications and used in cosmetics and personal care products.
ChEBI: The sulfonamide resulting from formal condensation of the sulfo group of 4-ethoxy-3-(5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one-2-yl)benzenesulfonic acid and the secondary amino group of 4-ethylpiperazine.
Flammability and Explosibility
Non flammable
Treatment of erectile dysfunction
Potentially hazardous interactions with other drugs
Alpha-blockers: enhanced hypotensive effect - avoid
for 6 hours after alpha-blockers (max dose 5 mg).
Antifungals: concentration increased by
ketoconazole, and itraconazole - avoid concomitant
use.
Antivirals: concentration increased by fosamprenavir,
indinavir and ritonavir- avoid with indinavir and
ritonavir; increased risk of ventricular arrhythmias
with saquinavir - avoid; avoid with telaprevir, use
tipranavir with caution.
Cobicistat: concentration of vardenafil possibly
increased - reduce dose of vardenafil.
Grapefruit juice: concentration possibly increased -
avoid concomitant use.
Nicorandil: possibly enhanced hypotensive effect -
avoid concomitant use.
Nitrates: possibly enhanced hypotensive effect -
avoid concomitant use.
Riociguat: enhanced hypotensive effect - avoid
concomitant use.
Vardenafil is metabolised in the liver primarily by
cytochrome P450 isoenzymes CYP3A4 (the major route)
as well as CYP3A5 and CYP2C isoforms. The major
metabolite produced by desethylation of vardenafil also
has some activity.
Vardenafil is excreted as metabolites mainly in the faeces
(91 to 95
%), and to a lesser extent in the urine.
