Details
Stereochemistry | ACHIRAL |
Molecular Formula | C22H19ClO3 |
Molecular Weight | 366.837 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC1=C([C@H]2CC[C@@H](CC2)C3=CC=C(Cl)C=C3)C(=O)C4=CC=CC=C4C1=O
InChI
InChIKey=KUCQYCKVKVOKAY-CTYIDZIISA-N
InChI=1S/C22H19ClO3/c23-16-11-9-14(10-12-16)13-5-7-15(8-6-13)19-20(24)17-3-1-2-4-18(17)21(25)22(19)26/h1-4,9-13,15,26H,5-8H2/t13-,15-
Molecular Formula | C22H19ClO3 |
Molecular Weight | 366.837 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Atovaquone is a chemical compound that belongs to the class of naphthoquinones; it is manufactured in the US in the liquid form, or oral suspension, under the brand name Mepron. Meron is used for the treatment or prevention of Pneumocystis carinii pneumonia in patients who are intolerant to trimethoprim-sulfamethoxazole (TMP-SMX). Also indicated for the acute oral treatment of mild to moderate PCP in patients who are intolerant to TMP-SMX. The mechanism of action against Pneumocystis jiroveci has not been fully elucidated. In Plasmodium species, the site of action appears to be the cytochrome bc1 complex (Complex III). Several metabolic enzymes are linked to the mitochondrial electron transport chain via ubiquinone. Inhibition of electron transport by atovaquone results in indirect inhibition of these enzymes. The ultimate metabolic effects of such blockade may include inhibition of nucleic acid and adenosine triphosphate (ATP) synthesis. Several laboratories, using different in vitro methodologies, have shown the IC50 (50% inhibitory concentration) of atovaquone against P. jiroveci to be 0.1 to 3.0 mcg/mL.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1777 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12791689 |
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Target ID: Q08210 Gene ID: 3885966.0 Gene Symbol: NA Target Organism: Plasmodium falciparum (isolate 3D7) Sources: https://www.ncbi.nlm.nih.gov/pubmed/7726490 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | MEPRON Approved Use1.1 Prevention of Pneumocystis jiroveci Pneumonia. MEPRON® suspension is indicated for the prevention of Pneumocystis jiroveci pneumonia (PCP) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprimsulfamethoxazole (TMP-SMX). 1.2 Treatment of Mild-to-Moderate Pneumocystis jiroveci Pneumonia
MEPRON suspension is indicated for the acute oral treatment of mild-to-mod Launch Date1992 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.1 μg/mL |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FED |
|
8.8 μg/mL |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
15.1 μg/mL |
500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
15.3 μg/mL |
750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
16.8 μg/mL |
1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
24 μg/mL |
750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
324 μg × h/mL |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
801 μg × h/mL |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FED |
|
280 μg × h/mL |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FED |
|
169 μg × h/mL |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.1% |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
0.1% |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FED |
|
0.1% |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FED |
|
0.1% |
500 mg 1 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
|
0.1% |
500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
0.1% |
750 mg 1 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
0.1% |
1000 mg 1 times / day steady-state, oral dose: 1000 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: FED |
|
0.1% |
750 mg 2 times / day steady-state, oral dose: 750 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
ATOVAQUONE plasma | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1000 mg 2 times / day multiple, oral Highest studied dose Dose: 1000 mg, 2 times / day Route: oral Route: multiple Dose: 1000 mg, 2 times / day Sources: |
unhealthy |
|
31500 mg single, oral Overdose Dose: 31500 mg Route: oral Route: single Dose: 31500 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
Other AEs: Methemoglobinemia, Rash... Other AEs: Methemoglobinemia Sources: Rash |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Rash, Diarrhea... AEs leading to discontinuation/dose reduction: Rash (grade 1-2, 6%) Sources: Diarrhea (4%) Nausea (3%) |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (4%) Sources: |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Vomiting, ALT increased... AEs leading to discontinuation/dose reduction: Vomiting (<1%) Sources: ALT increased (2%) Aspartate aminotransferase increase (2%) |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Creatinine increased, Blood urea nitrogen increased... AEs leading to discontinuation/dose reduction: Creatinine increased (1%) Sources: Blood urea nitrogen increased (1%) Amylase increased (1%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Methemoglobinemia | 31500 mg single, oral Overdose Dose: 31500 mg Route: oral Route: single Dose: 31500 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
|
Rash | 31500 mg single, oral Overdose Dose: 31500 mg Route: oral Route: single Dose: 31500 mg Sources: |
unhealthy Health Status: unhealthy Sources: |
|
Nausea | 3% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Diarrhea | 4% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rash | grade 1-2, 6% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Rash | 4% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
ALT increased | 2% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Aspartate aminotransferase increase | 2% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Vomiting | <1% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Amylase increased | 1% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Blood urea nitrogen increased | 1% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Creatinine increased | 1% Disc. AE |
1500 mg 1 times / day multiple, oral Recommended Dose: 1500 mg, 1 times / day Route: oral Route: multiple Dose: 1500 mg, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25218605/ |
no | |||
no | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25218605/ |
no | |||
no | ||||
weak | ||||
yes [IC50 0.23 uM] | ||||
yes [IC50 6.8 uM] | ||||
yes | ||||
yes | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/25218605/ |
yes | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/25218605/ |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Efficacy of a hydroxynaphthoquinone, 566C80, in experimental Pneumocystis carinii pneumonitis. | 1990 Feb |
|
566C80, an antimalarial hydroxynaphthoquinone with broad spectrum: experimental activity against opportunistic parasitic infections of AIDS patients. | 1991 Nov-Dec |
|
Relative potency of 10 drugs with anti-Pneumocystis carinii activity in an animal model. | 1994 Oct |
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Influence of antimicrobial agents on replication and stage conversion of Toxoplasma gondii. | 1996 |
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Chronic infection with Toxoplasma gondii does not prevent acute disease or colonization of the brain with tissue cysts following reinfection with different strains of the parasite. | 1997 Jun |
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Resistance mutations reveal the atovaquone-binding domain of cytochrome b in malaria parasites. | 1999 Aug |
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Synergistic effect of clindamycin and atovaquone in acute murine toxoplasmosis. | 1999 Sep |
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Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Sensitivity of Plasmodium vivax to chloroquine, mefloquine, artemisinin and atovaquone in north-western Thailand. | 2011 Oct |
|
Design, synthesis and biological evaluation of WC-9 analogs as antiparasitic agents. | 2013 Nov |
|
In vitro and in vivo combination of cepharanthine with anti-malarial drugs. | 2014 Mar 12 |
|
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
Patents
Sample Use Guides
Dosage for the Prevention of P. jiroveci Pneumonia:
1,500 mg (10 mL) once daily administered with food.
Dosage for the Treatment of Mild-to-Moderate P. jiroveci Pneumonia
The recommended oral dosage is 750 mg (5 mL) twice daily (total daily dose = 1,500 mg) administered with food for 21 days.
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:10:59 GMT 2025
by
admin
on
Mon Mar 31 18:10:59 GMT 2025
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Record UNII |
Y883P1Z2LT
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C277
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FDA ORPHAN DRUG |
48890
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FDA ORPHAN DRUG |
66692
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FDA ORPHAN DRUG |
48990
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NDF-RT |
N0000175482
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WHO-ATC |
P01AX06
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FDA ORPHAN DRUG |
66792
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LIVERTOX |
NBK548592
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NDF-RT |
N0000175485
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Code System | Code | Type | Description | ||
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ATOVAQUONE
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60212
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7083
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C28838
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m2127
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PRIMARY | Merck Index | ||
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DB01117
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CHEMBL1450
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6914
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Atovaquone
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Y883P1Z2LT
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D053626
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1044651
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Y883P1Z2LT
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100000086636
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Atovaquone and Proquanil
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95233-18-4
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575568
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EE-53
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759582
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258
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SUB05602MIG
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DTXSID7022629
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Related Record | Type | Details | ||
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BASIS OF STRENGTH->SUBSTANCE |
calculated on the anhydrous and organic solvent-free basis
ASSAY (HPLC)
USP
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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