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.
