Avanafil

Các tên gọi khác (3) :

(S)-4-(3-Chloro-4-methoxybenzylamino)-2-(2-hydroxymethylpyrrolidin-1-yl)-N-pyrimidin-2-ylmethyl-5-pyrimidinecarboxamide
Stendra
TA-1790

Thuốc Gốc

Small Molecule

CAS: 330784-47-9

CTHH: C₂₃H₂₆ClN₇O₃

PTK: 483.951

Avanafil is a new phosphodiesterase-5 inhibitor that is faster acting and more selective than other drugs belonging to the same class. Chemically, it is a derivative of pyrimidine and is only available as the S-enantiomer. FDA approved on April 27, 2012.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₂₃H₂₆ClN₇O₃

Phân tử khối

483.951

Monoisotopic mass

483.17856544

InChI

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

InChI Key

InChIKey=WEAJZXNPAWBCOA-INIZCTEOSA-N

IUPAC Name

4-{[(3-chloro-4-methoxyphenyl)methyl]amino}-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide

Traditional IUPAC Name

avanafil

SMILES

COC1=C(Cl)C=C(CNC2=C(C=NC(=N2)N2CCC[C@H]2CO)C(=O)NCC2=NC=CC=N2)C=C1

Độ hòa tan

2.97e-02 g/l

logP

2.78

logS

-4.2

pKa (strongest acidic)

12.53

pKa (Strongest Basic)

5.54

PSA

125.39 Å²

Refractivity

131.75 m³·mol^-1

Polarizability

50.87 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

MDDR-Like Rule

true

Dược Lực Học : Avanafil is a strong, competitive inhibitor of PDE5. It is also 100-times more potent for PDE5 than PDE6. The IC50 of avanafil is 5.2 nM. Compared to other PDE5 inhibitor like sildenafil and vardenafil, it is 16- and 21-fold more selective for PDE5 respectively. Avanafil does not bind to PDE6 and PDE11 to a considerable degree. The impact of this finding is that avanafil is less likely to cause side effects such as visual disturbances and myalgia. These are side effects that patients on sildenafil or tadalafil are more likely to experience. Furthermore, single oral doses of avanafil (200 mg) administered to healthy male volunteers resulted in mean changes from baseline in systolic/diastolic blood pressure of -5.3/-3.7 mmHg at 1 hour after dosing. Avanafil does not causes changes in QTc interval or ventricular repolarization.

Cơ Chế Tác Dụng : Avanafil is a new phosphodiesterase-5 inhibitor that is faster acting and more selective than other drugs belonging to the same class. Chemically, it is a derivative of pyrimidine and is only available as the S-enantiomer. FDA approved on April 27, 2012. Avanafil is a selective phosphodiesterase 5 (PDE5) enzyme inhibitor used for the treatment of erectile dysfunction caused by diabetes, age induced oxidative stress or other complications. Avanafil inhibits the cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum located around the penis. Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum. The inhibition of phosphodiesterase type 5 (PDE5) by avanafil enhances erectile function by increasing the amount of cGMP.

Dược Động Học :

▧ Absorption :
Avanafil is rapidly absorbed and does not accumulate following multiple doses. Tmax = 30 - 45 minutes; Time to peak response = 10 minutes (20 minutes shorter than sildenafil)
▧ Protein binding :
99% bound to plasma protein. Protein binding is independent of total drug concentrations, age, renal and hepatic function.
▧ Metabolism :
Avanafil is hepatically metabolized primarily by the enzyme, CYP3A4. Two major metabolites are formed, M4 and M16. M4 has 4% of the pharmacologic activity of avanafil. M16 is an inactive metabolite.
▧ Route of Elimination :
After oral administration, avanafil is excreted as metabolites predominantly in the feces (approximately 62% of administered oral dose) and to a lesser extent in the urine (approximately 21% of the administered oral dose).
▧ Half Life :
Mean elimination half-life = 5.36 - 10.66 hours

Độc Tính : Avanafil is generally well tolerated. The most commonly reported adverse event are headache and facial flushing.

Chỉ Định : Treatment of erectile dysfunction in males.

Tương Tác Thuốc :

Azilsartan medoxomil Pharmacodynamic synergist- increases effects.
Desipramine Co-administration with avanafil resulted in an approximate 5.7% increase in AUC0-inf and 5.2% decrease in Cmax of rosiglitazone.
Erythromycin Co-administration with the moderate CYP3A4 inhibitor erythromycin resulted in an approximate 3.6-fold increase in AUC0-inf and 2.0-fold increase in Cmax of avanafil.
Isosorbide Dinitrate Additive vasodilation. Concomitant therapy is contraindicated.
Isosorbide Mononitrate Additive vasodilation. Concomitant therapy is contraindicated.
Ketoconazole Co-administration with the strong CYP3A4 inhibitor ketoconazole resulted in an approximate 13-fold increase in AUC0-inf and 3.1-fold increase in Cmax.
Nitroglycerin Additive vasodilation. Concomitant therapy is contraindicated.
Omeprazole Nineteen healthy male volunteers received a single 40 omeprazole delayed-release capsule once daily for 8 days (Days 1-8), and a single 200 mg avanafil on Day 8. Twelve hour pharmacokinetics of omeprazole on Days 7 and 8 were compared. Co-administration with avanafil resulted in an approximate 5.9% increase in AUC0-inf and 8.6% increase in Cmax of omeprazole.
Ritonavir Co-administration with the strong CYP3A4 inhibitor ritonavir resulted in an approximate 13-fold increase in AUC0-inf and 2.4-fold increase in Cmax of avanafil.
Rosiglitazone Co-administration with avanafil resulted in an approximate 2.0% increase in AUC0-inf and 14% decrease in Cmax of rosiglitazone.
Warfarin Co-administration with avanafil resulted in an approximate 1.6% increase in AUC(0-inf) and 5.2% decrease in Cmax of S-warfarin.

Liều Lượng & Cách Dùng : Tablet - Oral - 50 mg; 100 mg; 200 mg

Dữ Kiện Thương Mại

Nhà Sản Xuất

Công ty : Vivus

Sản phẩm biệt dược : Stendra

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06237

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D03217

National Drug Code Directory

http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/62541-303-30

Wikipedia

http://en.wikipedia.org/wiki/Avanafil

RxList

http://www.rxlist.com/stendra-drug.htm

Drugs.com

http://www.drugs.com/mtm/avanafil.html

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