ATAZANAVIR

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 Search

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21567_reyataz_lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/15585441

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 Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 protease 35 Target ID: CHEMBL243 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18006837	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2003/21567_reyataz_lbl.pdf	Curative		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
4422 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
6129 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
2298 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
57039 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
14874 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
8.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: FED
18.1 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	300 mg 1 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: RITONAVIR	RITONAVIR	ATAZANAVIR plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED
6.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
14% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021567s026lbl.pdf	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 Dose: 30 g Route: oral Route: single Dose: 30 g Sources: https://pubmed.ncbi.nlm.nih.gov/29706057/	unhealthy, 40 years n = 1 Health Status: unhealthy Condition: human immunodeficiency virus Age Group: 40 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29706057/	Other AEs: Monomorphic ventricular tachycardia... Other AEs: Monomorphic ventricular tachycardia Sources: https://pubmed.ncbi.nlm.nih.gov/29706057/
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: https://pubmed.ncbi.nlm.nih.gov/15156449/	unhealthy, adult Health Status: unhealthy Condition: human immunodeficiency virus Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15156449/	Disc. AE: Jaundice... Other AEs: Blood bilirubin indirect... AEs leading to discontinuation/dose reduction: Jaundice (7%) Other AEs: Blood bilirubin indirect (33%) Sources: https://pubmed.ncbi.nlm.nih.gov/15156449/

AEs

AE	Significance	Dose	Population
Monomorphic ventricular tachycardia		30 g single, oral Overdose Dose: 30 g Route: oral Route: single Dose: 30 g Sources: https://pubmed.ncbi.nlm.nih.gov/29706057/	unhealthy, 40 years n = 1 Health Status: unhealthy Condition: human immunodeficiency virus Age Group: 40 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/29706057/
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: https://pubmed.ncbi.nlm.nih.gov/15156449/	unhealthy, adult Health Status: unhealthy Condition: human immunodeficiency virus Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15156449/
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: https://pubmed.ncbi.nlm.nih.gov/15156449/	unhealthy, adult Health Status: unhealthy Condition: human immunodeficiency virus Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/15156449/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 CYP3A4/5 278 CYP4A9/11 37 UGT1A1 204 P-gp 1461 OATP1B1 788 OATP1B3 706 BCRP 699	CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2E1 667 CYP2C19 991 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	no
CYP4A9/11 37	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	weak [IC50 29 uM]
OATP1B1 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20102298/	yes [IC50 1.7 uM]
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20102298/	yes [IC50 3 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	yes [IC50 4.9 uM]	BMS-551160 2
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/20102298/	yes [IC50 69.1 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	yes [Ki 12.1 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	yes [Ki 12.7 uM]
CYP3A4/5 335	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28,32	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%; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28,32
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=28 Page: 28.0	likely
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27.0	not significant
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27,29	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; Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_BioPharmr_P1.pdf#page=27 Page: 27,29

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-567_Reyataz_Pharmr_P1A.pdf#page=7 Page: 7.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:37924	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:37924
MolPort	MolPort-003-986-575	https://www.molport.com/shop/molecule-link/MolPort-003-986-575
ZINC	ZINC000003941496	http://zinc15.docking.org/substances/ZINC000003941496
eMolecules	32176608	https://www.emolecules.com/cgi-bin/more?vid=32176608

PubMed

Title	Date	PubMed
["Once daily" drugs simplify therapy. Rp. HAART once daily].	2003 Apr 28	15011606
[Highly effective drug without modifying the lipid profile. Atazanavir, the protease inhibitor for "once daily" administration].	2003 Apr 28	15011577
[Antiretroviral therapy 2003. The current status].	2003 Apr 28	15011574
The continuing evolution of HIV therapy.	2003 Dec	14959692
Gateways to clinical trials.	2003 Dec	14735233
[Are all boosted protease inhibitors the same? Previously treated patients profit too from lopinavir/r].	2003 Dec 11	14963981
Pharmacokinetics of amprenavir given once or twice a day when combined with atazanavir in heavily pre-treated HIV-positive patients.	2003 Dec 5	14685066
Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results.	2003 Dec 5	14685054
Drug profile: atazanavir (Reyataz, ATV).	2003 Jul	14696562
Atazanavir: clinical use.	2003 Jul	14696561
New anti-HIV protease inhibitors provide more treatment options.	2003 Nov	14746663
Atazanavir sulphate.	2003 Nov	14702957
Three new drugs approved by FDA.	2003 Nov-Dec	14696579
Atazanavir (Reyataz).	2003 Oct	14696568
FDA notifications. Reyataz is approved for HIV treatment.	2003 Sep	14686309
Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics.	2004	15217303
Peptidomimetic inhibitors of HIV protease.	2004	15193140
Cross-resistance patterns among HIV protease inhibitors.	2004 Apr	15142350
[Atazanavir protects lipid metabolism. New PI with favorable metabolic profile].	2004 Apr 26	15373065
[Good experiences with saquinavir. Double boosting of protease inhibitors gains significance].	2004 Apr 26	15373047
[Interview with Professor Jürgen Rockstroh, director of the Bonn University Clinic. Atazanavir in general practice].	2004 Apr 26	15373037
[Long-term tolerance. Favorable lipid profile--favorable effect on development of lipodystrophy?].	2004 Apr 26	15373036
[Simplified HIV therapy. Atazanavir: the first protease inhibitor with once daily administration].	2004 Apr 26	15373035
Regression of lipodystrophy in HIV-infected patients under therapy with the new protease inhibitor atazanavir.	2004 Apr 9	15060446
Resistance to HIV protease inhibitors: mechanisms and clinical consequences.	2004 Aug	15320704
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	15247553
Boosted Reyataz: 48-week results.	2004 Jan-Feb	15119279
Atazanavir: a new protease inhibitor to treat HIV infection.	2004 Jul 1	15287232
Acute hepatic cytolysis in an HIV-infected patient taking atazanavir.	2004 Jul 23	15238786
Gateways to clinical trials.	2004 Jul-Aug	15349141
The influence of protease inhibitor resistance profiles on selection of HIV therapy in treatment-naive patients.	2004 Jun	15259893
Antiviral drugs in current clinical use.	2004 Jun	15125867
Long-term efficacy and safety of atazanavir with stavudine and lamivudine in patients previously treated with nelfinavir or atazanavir.	2004 Jun 1	15167287
Atazanavir: new option for treatment of HIV infection.	2004 Jun 1	15156449
Atazanavir enhances saquinavir hard-gel concentrations in a ritonavir-boosted once-daily regimen.	2004 Jun 18	15362661
Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors.	2004 Mar 1	14986280
Atazanavir (Reyataz): new recommendations if combined with tenofovir (Viread) -- and warning on Viagra, Cialis, and Levitra.	2004 Mar 26	15199867
Optimizing dosing strategies for the combination of atazanavir plus saquinavir.	2004 Mar 5	15090782
Initial therapy for human immunodeficiency virus: broadening the options.	2004 Mar-Apr	15116286
New drugs of 2003.	2004 Mar-Apr	15098851
Kinetic and thermodynamic characterization of HIV-1 protease inhibitors.	2004 Mar-Apr	15027031
Gateways to clinical trials.	2004 May	15319808
Does atazanavir cause lipodystrophy?	2004 May	15238875
Identification of I50L as the signature atazanavir (ATV)-resistance mutation in treatment-naive HIV-1-infected patients receiving ATV-containing regimens.	2004 May 15	15122516
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	15081931
[New treatment options for HIV-infected patients].	2004 May 7	15174468
Atazanavir.	2004 Oct	15353575
Pseudoaneurysm of the femoral artery in a HIV-infected man.	2004 Oct	15350573
Determination of the new HIV-protease inhibitor atazanavir by liquid chromatography after solid-phase extraction.	2004 Oct 15	15358304
HIV-chemotherapy and -prophylaxis: new drugs, leads and approaches.	2004 Sep	15183346

Patents

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.

Name

Type

Language

ATAZANAVIR

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