Atazanavir Chemische Eigenschaften,Einsatz,Produktion Methoden
Chemische Eigenschaften
Crystalline Solid
Verwenden
Atazanavir is a novel azapeptide protease inhibitor (PI)
Definition
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).
Acquired resistance
Mutations at positions 50 (I50L), 84 (I84V) and 88 (N88S)
of the protease gene are associated with resistance.
Allgemeine Beschreibung
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.
Pharmazeutische Anwendungen
An azapeptide formulated as the sulfate for oral use.
Mechanism of action
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.
Pharmakokinetik
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.
Clinical Use
Treatment of HIV infection (in combination with other antiretroviral drugs)
Nebenwirkungen
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.
Atazanavir Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte