ABT-333 Chemical Properties

Melting point:

>192oC (dec.)

Density 

1.317±0.06 g/cm3(Predicted)

storage temp. 

Hygroscopic, -20°C Freezer, Under inert atmosphere

solubility 

Chloroform (Slightly, Heated), DMSO (Slightly), Methanol (Slightly, Heated)

pka

8.52±0.30(Predicted)

form 

Solid

color 

Pale Brown to Light Brown

ABT-333 Usage And Synthesis

Uses

Dasabuvir is an antiviral drug used in the treatment of chronic hepatitis C virus (HCV) infection.

Definition

ChEBI: A member of the class of pyrimidone, which is (as the monohydrate of its sodium salt) in combination with ombitasvir, paritaprevir and ritonavir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as c rrhosis of the liver.

Clinical Use

Treatment of chronic hepatitis C infection

Drug interactions

Potentially hazardous interactions with other drugs
Antibacterials: avoid concomitant use with clarithromycin and telithromycin; concentration possibly reduced by rifampicin - avoid.
Antidepressants: concentration possibly reduced by St John’s wort - avoid.
Antiepileptics: concentration reduced by carbamazepine - avoid; concentration possibly reduced by fosphenytoin, phenobarbital, phenytoin and primidone - avoid.
Antifungals: concentration of both drugs increased with ketoconazole and possibly itraconazole and posaconazole - avoid.
Diuretics: concentration of furosemide increased (reduce furosemide dose).
Immunosuppressants: increases concentration of ciclosporin (reduce ciclosporin dose by a fifth); everolimus (avoid); sirolimus and tacrolimus (reduce dose and use only if benefit outweighs risk - see SPC).
Lipid-regulating drugs: avoid with atorvastatin, gemfibrozil and simvastatin; concentration of rosuvastatin increased (reduce dose of rosuvastatin).
Oestrogens: avoid concomitant use with ethinylestradiol.

Metabolism

Dasabuvir is mainly metabolised by CYP2C8 and to a lesser extent by CYP3A. Seven metabolites were identified in plasma. The most abundant plasma metabolite was M1, which represented 21% of drugrelated radioactivity (AUC) in circulation following single dose; it is formed via oxidative metabolism predominantly by CYP2C8.
Following a 400 mg 14C-dasabuvir dose, approximately 94% of the radioactivity was recovered in faeces with limited radioactivity (approximately 2%) in urine. Unchanged dasabuvir accounted for 26.2% and M1 for 31.5% of the total dose in faeces. M1 is mainly cleared through direct biliary excretion with the contribution of UGT-mediated glucuronidation and, to a small extent, oxidative metabolism.