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Details

Stereochemistry ABSOLUTE
Molecular Formula C23H26ClN7O3
Molecular Weight 483.951
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AVANAFIL

SMILES

COC1=C(Cl)C=C(CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCC[C@H]4CO)C=C1

InChI

InChIKey=WEAJZXNPAWBCOA-INIZCTEOSA-N
InChI=1S/C23H26ClN7O3/c1-34-19-6-5-15(10-18(19)24)11-27-21-17(22(33)28-13-20-25-7-3-8-26-20)12-29-23(30-21)31-9-2-4-16(31)14-32/h3,5-8,10,12,16,32H,2,4,9,11,13-14H2,1H3,(H,28,33)(H,27,29,30)/t16-/m0/s1

HIDE SMILES / InChI

Description

Avanafil is a PDE5 inhibitor approved for erectile dysfunction by FDA and by EMA. Avanafil is known by the trademark names Stendra and Spedra and was developed by Vivus Inc. Avanafil selectively inhibits PDE5, thus inhibiting the degradation of cyclic guanosine monophosphate (cGMP) found in the smooth muscle of the corpus cavernosa of the penis. The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Avanafil has no direct relaxant effect on isolated human corpus cavernosum, but enhances the effect of NO by inhibiting PDE5, which is responsible for degradation of cGMP in the corpus cavernosum. Because sexual stimulation is required to initiate the local release of nitric oxide, the inhibition of PDE5 has noeffect in the absence of sexual stimulation. The advantage of avanafil is that it has very fast onset of action compared with other PDE5 inhibitors. It is absorbed quickly, reaching a maximum concentration in about 30–45 minutes. About two-thirds of the participants were able to engage in sexual activity within 15 minutes.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
5.2 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
STENDRA

Cmax

ValueDoseCo-administeredAnalytePopulation
2630 ng/mL
100 mg single, oral
AVANAFIL plasma
Homo sapiens
2231.63 ng/mL
100 mg 1 times / day steady-state, oral
[NO STEREO] AVANAFIL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
7148.67 ng × h/mL
100 mg single, oral
AVANAFIL plasma
Homo sapiens
7339.13 ng × h/mL
100 mg 1 times / day steady-state, oral
[NO STEREO] AVANAFIL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
7.53 h
100 mg single, oral
AVANAFIL plasma
Homo sapiens
8.66 h
100 mg 1 times / day steady-state, oral
[NO STEREO] AVANAFIL plasma
Homo sapiens
5 h
single, oral
AVANAFIL plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
single, oral
AVANAFIL plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The starting dose is 100 mg taken as early as approximately 15 minutes before sexual activity, on an as needed basis. Take STENDRA no more than once a day. Based on efficacy and/or tolerability, the dose may be increased to 200 mg taken as early as approximately 15 minutes before sexual activity, or decreased to 50 mg taken approximately 30 minutes before sexual activity. Use the lowest dose that provides benefit. May be taken with or without food.
Route of Administration: Oral
In Vitro Use Guide
Unknown