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
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
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
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18006837 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | REYATAZ Approved UseREYATAZ® (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 Date2003 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
30 g single, oral Overdose |
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... |
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
AE | Significance | Dose | Population |
---|---|---|---|
Monomorphic ventricular tachycardia | 30 g single, oral Overdose |
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: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/15764714
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.
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Classification Tree | Code System | Code | ||
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WHO-ATC |
J05AR15
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WHO-VATC |
QJ05AE08
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WHO-ESSENTIAL MEDICINES LIST |
6.4.2.3
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WHO-ATC |
J05AR23
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NCI_THESAURUS |
C97366
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LIVERTOX |
NBK547918
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NDF-RT |
N0000000246
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WHO-ATC |
J05AE08
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NDF-RT |
N0000175889
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148192
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C413408
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198904-31-3
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QZU4H47A3S
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N0000191269
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PRIMARY | UDP Glucuronosyltransferases Inhibitors [MoA] | ||
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ATAZANAVIR
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SUB16398MIG
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C66872
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37924
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N0000182141
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PRIMARY | Cytochrome P450 3A4 Inhibitors [MoA] | ||
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254
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N0000187062
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PRIMARY | Cytochrome P450 2C8 Inhibitors [MoA] | ||
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8181
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DB01072
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m2119
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PRIMARY | Merck Index | ||
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Atazanavir
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343047
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PRIMARY | RxNorm | ||
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7339
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DTXSID9048691
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QZU4H47A3S
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CHEMBL1163
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100000089517
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N0000190114
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PRIMARY | Cytochrome P450 3A Inhibitors [MoA] | ||
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N0000191272
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PRIMARY | UGT1A1 Inhibitors [MoA] |
ACTIVE MOIETY
SALT/SOLVATE (PARENT)