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

2003
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
BMS-232632, a highly potent human immunodeficiency virus protease inhibitor that can be used in combination with other available antiretroviral agents.
2000 Aug
In vitro resistance profile of the human immunodeficiency virus type 1 protease inhibitor BMS-232632.
2000 Sep
[Progress toward a once daily regimen. (HA)ART--the art of antiretroviral therapy].
2001 Apr 2
Promising new agents on the horizon.
2002 Mar
Gateways to clinical trials.
2002 Oct
Gateways to Clinical Trials.
2002 Sep
[Are all boosted protease inhibitors the same? Previously treated patients profit too from lopinavir/r].
2003 Dec 11
[Highly effective and tolerable protease inhibitor. New trump card against HIV].
2003 Jan 16
Gateways to clinical trials.
2003 Jan-Feb
Application of the Lewis acid-Lewis base bifunctional asymmetric catalysts to pharmaceutical syntheses: stereoselective chiral building block syntheses of human immunodeficiency virus (HIV) protease inhibitor and beta3-adenergic receptor agonist.
2003 Jun
Reviving protease inhibitors: new data and more options.
2003 Jun 1
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 background documents available.
2003 May 30
Three new drugs approved by FDA.
2003 Nov-Dec
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
First once-daily protease inhibitor.
2003 Sep-Oct
Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics.
2004
Peptidomimetic inhibitors of HIV protease.
2004
Cross-resistance patterns among HIV protease inhibitors.
2004 Apr
[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
[Long-term tolerance. Favorable lipid profile--favorable effect on development of lipodystrophy?].
2004 Apr 26
Comparison of once-daily atazanavir with efavirenz, each in combination with fixed-dose zidovudine and lamivudine, as initial therapy for patients infected with HIV.
2004 Aug 15
Acute hepatic cytolysis in an HIV-infected patient taking atazanavir.
2004 Jul 23
Long-term efficacy and safety of atazanavir with stavudine and lamivudine in patients previously treated with nelfinavir or atazanavir.
2004 Jun 1
Atazanavir: new option for treatment of HIV infection.
2004 Jun 1
Atazanavir (Reyataz): new recommendations if combined with tenofovir (Viread) -- and warning on Viagra, Cialis, and Levitra.
2004 Mar 26
New drugs of 2003.
2004 Mar-Apr
Gateways to clinical trials.
2004 May
Does atazanavir cause lipodystrophy?
2004 May
Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens.
2004 May 15
Simultaneous quantification of the new HIV protease inhibitors atazanavir and tipranavir in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
2004 May 25
[New treatment options for HIV-infected patients].
2004 May 7
Determination of the new HIV-protease inhibitor atazanavir by liquid chromatography after solid-phase extraction.
2004 Oct 15
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.
2004 Sep
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 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
WHO-VATC QJ05AE08
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
WHO-ESSENTIAL MEDICINES LIST 6.4.2.3
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
WHO-ATC J05AR23
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
NCI_THESAURUS C97366
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
LIVERTOX NBK547918
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
NDF-RT N0000000246
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
WHO-ATC J05AE08
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
NDF-RT N0000175889
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
Code System Code Type Description
PUBCHEM
148192
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
MESH
C413408
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
CAS
198904-31-3
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
DAILYMED
QZU4H47A3S
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
NDF-RT
N0000191269
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY UDP Glucuronosyltransferases Inhibitors [MoA]
WIKIPEDIA
ATAZANAVIR
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
EVMPD
SUB16398MIG
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
NCI_THESAURUS
C66872
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
CHEBI
37924
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
NDF-RT
N0000182141
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
DRUG CENTRAL
254
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
NDF-RT
N0000187062
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY Cytochrome P450 2C8 Inhibitors [MoA]
INN
8181
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
DRUG BANK
DB01072
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
MERCK INDEX
m2119
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY Merck Index
LACTMED
Atazanavir
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
RXCUI
343047
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY RxNorm
HSDB
7339
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID9048691
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
FDA UNII
QZU4H47A3S
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
ChEMBL
CHEMBL1163
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
SMS_ID
100000089517
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY
NDF-RT
N0000190114
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY Cytochrome P450 3A Inhibitors [MoA]
NDF-RT
N0000191272
Created by admin on Sat Dec 16 15:48:42 GMT 2023 , Edited by admin on Sat Dec 16 15:48:42 GMT 2023
PRIMARY UGT1A1 Inhibitors [MoA]