Атазанавир

Химические свойства

Crystalline Solid

Использование

Atazanavir is a novel azapeptide protease inhibitor (PI)

Определение

ChEBI: A heavily substituted carbohydrazide that is an antiretroviral drug of the protease inhibitor (PI) class used to treat infection of human immunodeficiency virus (HIV).

Приобретенная устойчивость

Mutations at positions 50 (I50L), 84 (I84V) and 88 (N88S) of the protease gene are associated with resistance.

Общее описание

Atazanavir is an antiretroviral agent that has been approvedby the FDA for use in combination with other anti-RTagents for the treatment of HIV infections. The drug is alwaysused in combination with RT inhibitors.

Фармацевтические приложения

An azapeptide formulated as the sulfate for oral use.

Механизм действия

Atazanavir is dosed orally once daily, thus reducing "pill burden," and it appears to have minimal impact on lipid parameters but does increase total bilirubin. The drug is well absorbed when administered orally with food (bioavailability, ~68%). The drug is highly bound to plasma protein (86%) and is metabolized by CYP3A isoenzyme. Atazanavir is a moderate inhibitor of CYP3A, and potential drug–drug interactions are possible with CYP3A inhibitors and inducers.

Фармакокине?тика

Oral absorption: c. 68%
C_max 400 mg once daily: c. 3.15 μg/L
300 mg + ritonavir 100 mg once daily: c. 4.47 μg/L
C_min 400 mg once daily: c. 0.27 μg/L
300 mg + ritonavir 100 mg once daily: c. 0.65 μg/L
Plasma half-life: c. 8.6 h (300 mg+ ritonavir 100 mg)
Volume of distribution: c. Not known/available
Plasma protein binding: c. 86%
Absorption
Administration with food enhances bioavailability and reduces pharmacokinetic variability. Absorption is dependent on gastric pH. It should be given separately from proton-pump inhibitors or H2-receptor antagonists. Buffered or entericcoated formulations should be given (with food) 2 h before or 1 h after co-administration of didanosine.
Distribution
It penetrates moderately well into the CNS. The semen:plasma ratio is 0.11–4.42. It is distributed into breast milk.
Metabolism
It is extensively metabolized by CYP3A4. Administration with ritonavir prevents metabolization and enhances the pharmacokinetic profile.
Excretion
Following a single 400 mg dose, 79% and 13% of the dose was recovered in the feces and urine, respectively. It should be used with caution in the presence of mild hepatic impairment and should not be used in patients with more severe hepatic impairment.

Клиническое использование

Treatment of HIV infection (in combination with other antiretroviral drugs)

Побочные эффекты

The most common adverse reactions (≥2%) are nausea, jaundice/ scleral icterus, rash, headache, abdominal pain, vomiting, insomnia, peripheral neurological symptoms, dizziness, myalgia, diarrhea, depression and fever.