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Details

Stereochemistry ABSOLUTE
Molecular Formula C38H52N6O7
Molecular Weight 704.8555
Optical Activity ( - )
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ATAZANAVIR

SMILES

COC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)[C@@H](O)CN(CC2=CC=C(C=C2)C3=CC=CC=N3)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C(C)(C)C

InChI

InChIKey=AXRYRYVKAWYZBR-GASGPIRDSA-N
InChI=1S/C38H52N6O7/c1-37(2,3)31(41-35(48)50-7)33(46)40-29(22-25-14-10-9-11-15-25)30(45)24-44(43-34(47)32(38(4,5)6)42-36(49)51-8)23-26-17-19-27(20-18-26)28-16-12-13-21-39-28/h9-21,29-32,45H,22-24H2,1-8H3,(H,40,46)(H,41,48)(H,42,49)(H,43,47)/t29-,30-,31+,32+/m0/s1

HIDE SMILES / InChI

Molecular Formula C38H52N6O7
Molecular Weight 704.8555
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Atazanavir is the first once-daily protease inhibitor for the treatment of human immunodeficiency virus type 1 infection and should be used only in combination therapy, as part of a highly active antiretroviral therapy (HAART) regimen. In addition to being the most potent protease inhibitor in vitro, atazanavir has a distinct cross-resistance profile that does not confer resistance to other protease inhibitors. However, resistance to other protease inhibitors often confers clinically relevant resistance to atazanavir.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
REYATAZ

Cmax

ValueDoseCo-administeredAnalytePopulation
4422 ng/mL
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
6129 ng/mL
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
2298 ng/mL
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
5199 ng/mL
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
46073 ng × h/mL
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
57039 ng × h/mL
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
14874 ng × h/mL
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
28132 ng × h/mL
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
8.6 h
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
18.1 h
300 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
6.5 h
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens
7.9 h
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
14%
400 mg 1 times / day steady-state, oral
ATAZANAVIR plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
The recommended dose of REYATAZ ((atazanavir sulfate) capsules) is 400 mg (two 200-mg capsules) once daily taken with food. When coadministered with efavirenz, it is recommended that REYATAZ 300 mg and ritonavir 100 mg be given with efavirenz 600 mg (all as a single daily dose with food). REYATAZ without ritonavir should not be coadministered with efavirenz. When coadministered with didanosine buffered formulations, 589 REYATAZ should be given (with food) 2 hours before or 1 hour after didanosine.
Route of Administration: Oral
In Vitro Use Guide
It was investigated the effect of atazanavir on P-glycoprotein (P-gp) expression and activity, as well as its inhibitory potency against CYP3A activity. Induction of P-gp activity and expression was studied using LS180V cells. P-gp inhibition was studied using both LS180V cells and Caco-2 cells. Extended (3-day) exposure of LS180V cells to 30 microM atazanavir caused a 2.5-fold increase in immunoreactive P-gp expression as well as a concentration-dependent decrease of intracellular Rh123 to a mean 45% (S.D. 5.2%) of control. Acute exposure (2 h) of LS180V cells to atazanavir increased intracellular Rh123 concentrations up to 300% of control at 100 microM atazanavir. At 30 microM and above, acute atazanavir exposure reversed P-gp induction caused by 3-day pretreatment with 10 microM ritonavir. P-gp inhibition was also observed in Caco-2 cells, causing an effect comparable to that observed for the known P-gp inhibitor verapamil (50% of control). In HLM, atazanavir was an inhibitor of triazolam hydroxylation, with inhibitory potency greatly increased by preincubation. IC50 values with and without preincubation were 0.31 microM (S.D. 0.13) and 5.7 microM (S.D. 4.1), respectively.
Substance Class Chemical
Record UNII
QZU4H47A3S
Record Status Validated (UNII)
Record Version