U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
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.

Originator

Curator's Comment: # Novartis (before Ciba-Geigy)

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
REYATAZ

Approved Use

REYATAZ® (atazanavir sulfate) is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from controlled studies of 96 weeks duration in antiretroviral-naive and 48 weeks duration in antiretroviral-treatment-experienced adult and pediatric patients at least 6 years of age. The following points should be considered when initiating therapy with REYATAZ: In Study AI424-045, REYATAZ/ritonavir and lopinavir/ritonavir were similar for the primary efficacy outcome measure of time-averaged difference in change from baseline in HIV RNA level. This study was not large enough to reach a definitive conclusion that REYATAZ/ritonavir and lopinavir/ritonavir are equivalent on the secondary efficacy outcome measure of proportions below the HIV RNA lower limit of detection [see Clinical Studies (14.2)

Launch Date

1.05606722E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4422 ng/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
6129 ng/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
2298 ng/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
5199 ng/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
46073 ng × h/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
57039 ng × h/mL
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
14874 ng × h/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
28132 ng × h/mL
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.6 h
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
18.1 h
300 mg 1 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: RITONAVIR
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
6.5 h
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
7.9 h
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
14%
400 mg 1 times / day steady-state, oral
dose: 400 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ATAZANAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FED
Doses

Doses

DosePopulationAdverse events​
30 g single, oral
Overdose
Dose: 30 g
Route: oral
Route: single
Dose: 30 g
Sources:
unhealthy, 40 years
n = 1
Health Status: unhealthy
Condition: human immunodeficiency virus
Age Group: 40 years
Sex: M
Population Size: 1
Sources:
Other AEs: Monomorphic ventricular tachycardia...
Other AEs:
Monomorphic ventricular tachycardia
Sources:
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: human immunodeficiency virus
Age Group: adult
Sex: M+F
Sources:
Disc. AE: Jaundice...
Other AEs: Blood bilirubin indirect...
AEs leading to
discontinuation/dose reduction:
Jaundice (7%)
Other AEs:
Blood bilirubin indirect (33%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Monomorphic ventricular tachycardia
30 g single, oral
Overdose
Dose: 30 g
Route: oral
Route: single
Dose: 30 g
Sources:
unhealthy, 40 years
n = 1
Health Status: unhealthy
Condition: human immunodeficiency virus
Age Group: 40 years
Sex: M
Population Size: 1
Sources:
Blood bilirubin indirect 33%
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: human immunodeficiency virus
Age Group: adult
Sex: M+F
Sources:
Jaundice 7%
Disc. AE
400 mg 1 times / day steady, oral
Recommended
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Condition: human immunodeficiency virus
Age Group: adult
Sex: M+F
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
weak [IC50 29 uM]
yes [IC50 1.7 uM]
yes [IC50 3 uM]
yes [IC50 4.9 uM]
yes [IC50 69.1 uM]
yes [Ki 12.1 uM]
yes [Ki 12.7 uM]
yes [Ki 2.35 uM]
yes (co-administration study)
Comment: competitive and mechanism-based inhibition; administration with clarithromycin increased clarithromycin AUC by 94% and reduced 14-OH clarithromycin by 70; atazanavir increased diltiazem concentration by ~100%;
Page: 28,32
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
not significant
not significant
not significant
not significant
not significant
not significant
not significant
yes
yes (co-administration study)
Comment: 100% and 71% inhibition of ketonconazole and troleandomycin, respectively; administration with ritonavir increased atazanavir Cmax, AUC, and Cmin by 17%, 103%, and 671%, respectively;
Page: 27,29
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
New antiretroviral agents.
2001 Mar
A new protease inhibitor from Bristol-Myers Squibb.
2001 Spring
Gateways to Clinical Trials.
2002 Apr
Overcoming obstacles to the success of protease inhibitors in highly active antiretroviral therapy regimens.
2002 Dec
In vitro antiviral interaction of lopinavir with other protease inhibitors.
2002 Jul
Drug giant Bristol-Myers Squibb: Atazanavir moves into the spotlight while O83 bites the dust.
2002 Jul-Aug
Promising new agents on the horizon.
2002 Mar
Gateways to clinical trials.
2002 Nov
Gateways to clinical trials.
2002 Oct
Gateways to Clinical Trials.
2002 Sep
[Highly effective drug without modifying the lipid profile. Atazanavir, the protease inhibitor for "once daily" administration].
2003 Apr 28
[Are all boosted protease inhibitors the same? Previously treated patients profit too from lopinavir/r].
2003 Dec 11
Anti-HIV drug updates--three drugs on the near horizon.
2003 Jan
Gateways to clinical trials.
2003 Jan-Feb
Atazanavir gets FDA Advisory Committee's thumbs-up.
2003 Jun
Gateways to clinical trials. March 2003.
2003 Mar
New antiretroviral drugs.
2003 Mar
Distinct cross-resistance profiles of the new protease inhibitors amprenavir, lopinavir, and atazanavir in a panel of clinical samples.
2003 May 23
Quantitative determination of the HIV protease inhibitor atazanavir (BMS-232632) in human plasma by liquid chromatography-tandem mass spectrometry following automated solid-phase extraction.
2003 May 25
Atazanavir (Reyataz).
2003 Oct
Gateways to clinical trials.
2003 Oct
Liquid chromatography-tandem mass spectrometric quantitative determination of the HIV protease inhibitor atazanavir (BMS-232632) in human peripheral blood mononuclear cells (PBMC): practical approaches to PBMC preparation and PBMC assay design for high-throughput analysis.
2003 Oct 5
[Atazanavir--first protease inhibitor for one dose administration].
2003 Sep 26
First once-daily protease inhibitor.
2003 Sep-Oct
Peptidomimetic inhibitors of HIV protease.
2004
[Atazanavir protects lipid metabolism. New PI with favorable metabolic profile].
2004 Apr 26
[Good experiences with saquinavir. Double boosting of protease inhibitors gains significance].
2004 Apr 26
[Interview with Professor Jürgen Rockstroh, director of the Bonn University Clinic. Atazanavir in general practice].
2004 Apr 26
Resistance to HIV protease inhibitors: mechanisms and clinical consequences.
2004 Aug
Boosted Reyataz: 48-week results.
2004 Jan-Feb
Atazanavir: a new protease inhibitor to treat HIV infection.
2004 Jul 1
Gateways to clinical trials.
2004 Jul-Aug
The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients.
2004 Jun
Antiviral drugs in current clinical use.
2004 Jun
Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors.
2004 Mar 1
Initial therapy for human immunodeficiency virus: broadening the options.
2004 Mar-Apr
Gateways to clinical trials.
2004 May
Atazanavir.
2004 Oct
Pseudoaneurysm of the femoral artery in a HIV-infected man.
2004 Oct
Patents

Sample Use Guides

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
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.
Name Type Language
ATAZANAVIR
HSDB   INN   MI   VANDF   WHO-DD  
INN  
Official Name English
atazanavir [INN]
Common Name English
CGP-73547
Code English
BMS-232632
Code English
2,5,6,10,13-Pentaazatetradecanedioic acid, 3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-, 1,14-dimethyl ester, (3S,8S,9S,12S)-
Systematic Name English
ATAZANAVIR [VANDF]
Common Name English
ATAZANAVIR [MI]
Common Name English
DIMETHYL (3S,8S,9S,12S)-9-BENZYL-3,12,DI-TERT-BUTYL-8-HYDROXY-4,11-DIOXO-6-(P-2-PYRIDYLBENZYL)-2,5,6,10,13-PENTAAZATETRADECANEDIOATE
Common Name English
ATAZANAVIR [HSDB]
Common Name English
Atazanavir [WHO-DD]
Common Name English
1,14-Dimethyl (3S,8S,9S,12S)-3,12-bis(1,1-dimethylethyl)-8-hydroxy-4,11-dioxo-9-(phenylmethyl)-6-[[4-(2-pyridinyl)phenyl]methyl]-2,5,6,10,13-pentaazatetradecanedioate
Systematic Name English
Classification Tree Code System Code
WHO-ATC J05AR15
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
WHO-VATC QJ05AE08
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
WHO-ESSENTIAL MEDICINES LIST 6.4.2.3
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
WHO-ATC J05AR23
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
NCI_THESAURUS C97366
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
LIVERTOX NBK547918
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
NDF-RT N0000000246
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
WHO-ATC J05AE08
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
NDF-RT N0000175889
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
Code System Code Type Description
PUBCHEM
148192
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
MESH
C413408
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
CAS
198904-31-3
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
DAILYMED
QZU4H47A3S
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
NDF-RT
N0000191269
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY UDP Glucuronosyltransferases Inhibitors [MoA]
WIKIPEDIA
ATAZANAVIR
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
EVMPD
SUB16398MIG
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
NCI_THESAURUS
C66872
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
CHEBI
37924
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
NDF-RT
N0000182141
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
DRUG CENTRAL
254
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
NDF-RT
N0000187062
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
INN
8181
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
DRUG BANK
DB01072
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
MERCK INDEX
m2119
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY Merck Index
LACTMED
Atazanavir
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
RXCUI
343047
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY RxNorm
HSDB
7339
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
EPA CompTox
DTXSID9048691
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
FDA UNII
QZU4H47A3S
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
ChEMBL
CHEMBL1163
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
SMS_ID
100000089517
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
NDF-RT
N0000191272
Created by admin on Sat Dec 16 15:48:42 UTC 2023 , Edited by admin on Sat Dec 16 15:48:42 UTC 2023
PRIMARY UGT1A1 Inhibitors [MoA]