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Details

Stereochemistry ACHIRAL
Molecular Formula C11H16ClN5.H2O4S
Molecular Weight 351.81
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROGUANIL SULFATE

SMILES

OS(O)(=O)=O.CC(C)NC(=N)NC(=N)NC1=CC=C(Cl)C=C1

InChI

InChIKey=KKHARIGWPVRJRS-UHFFFAOYSA-N
InChI=1S/C11H16ClN5.H2O4S/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9;1-5(2,3)4/h3-7H,1-2H3,(H5,13,14,15,16,17);(H2,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula H2O4S
Molecular Weight 98.078
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C11H16ClN5
Molecular Weight 253.731
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Proguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. Proguanil in combination with atovaquone are marked under the brand name malarone, which is indicated for the treatment of acute, uncomplicated P. falciparum malaria and for the prophylaxis of Plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. Atovaquone and proguanil, interfere with 2 different pathways involved in the biosynthesis of pyrimidines required for nucleic acid replication. Atovaquone is a selective inhibitor of parasite mitochondrial electron transport. Proguanil hydrochloride primarily exerts its effect by means of the metabolite cycloguanil, a dihydrofolate reductase inhibitor. Inhibition of dihydrofolate reductase in the malaria parasite disrupts deoxythymidylate synthesis. Recently were done experiments, which confirmed the hypothesis that proguanil might act on another target than dihydrofolate reductase. In addition, was made conclusion, that effectiveness of malarone was due to the synergism between atovaquone and proguanil and may not require the presence of cycloguanil.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
MALARONE

Approved Use

Prevention of Malaria: Atovaquone and proguanil hydrochloride tablets are indicated for the prophylaxis of P. falciparum malaria, including in areas where chloroquine resistance has been reported (see CLINICAL STUDIES). Treatment of Malaria: Atovaquone and proguanil hydrochloride tablets are indicated for the treatment of acute, uncomplicated P. falciparum malaria. Atovaquone and proguanil hydrochloride tablets have been shown to be effective in regions where the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may have unacceptable failure rates, presumably due to drug resistance.

Launch Date

9.6353282E11
Preventing
MALARONE

Approved Use

Prevention of Malaria: Atovaquone and proguanil hydrochloride tablets are indicated for the prophylaxis of P. falciparum malaria, including in areas where chloroquine resistance has been reported (see CLINICAL STUDIES). Treatment of Malaria: Atovaquone and proguanil hydrochloride tablets are indicated for the treatment of acute, uncomplicated P. falciparum malaria. Atovaquone and proguanil hydrochloride tablets have been shown to be effective in regions where the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may have unacceptable failure rates, presumably due to drug resistance.

Launch Date

9.6353282E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
39 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
(4-CHLOROPHENYL)BIGUANIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
10 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
(4-CHLOROPHENYL)BIGUANIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
980 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
170 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
190 ng/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
209 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
50 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
CYCLOGUANIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
41 ng/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
CYCLOGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
883 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
(4-CHLOROPHENYL)BIGUANIDE blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
249 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
(4-CHLOROPHENYL)BIGUANIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
14070 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2975 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
141 μg × min/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CYCLOGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
834 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
CYCLOGUANIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
190 μg × min/mL
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CYCLOGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
661 ng × h/mL
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
CYCLOGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
15.7 h
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
16.1 h
3.5 mg/kg bw single, oral
dose: 3.5 mg/kg bw
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
21 h
200 mg 1 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
18 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROGUANIL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day multiple, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Co-administed with::
chloroquine(155 mg; oral; 2/week)
Sources: Page: p.1891
healthy, 13–74
n = 511
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 13–74
Sex: M+F
Population Size: 511
Sources: Page: p.1891
Disc. AE: Abdominal pain, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (0.98%)
Diarrhea (0.78%)
Nausea (1.17%)
Vomiting (0.39%)
Sources: Page: p.1891
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
atovaquone(250 mg oral; 1/day)
Sources: Page: p.745
healthy, 16 - 65
n = 175
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 16 - 65
Sex: M+F
Population Size: 175
Sources: Page: p.745
Disc. AE: Headache...
AEs leading to
discontinuation/dose reduction:
Headache (1.14%)
Sources: Page: p.745
150 mg 1 times / day multiple, oral (max)
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Co-administed with::
chloroquine(77.5-310 mg; oral; 1/week)
Sources: Page: p.1720
healthy, 3–16
n = 111
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 3–16
Sex: M+F
Population Size: 111
Sources: Page: p.1720
Disc. AE: Abdominal pain, Nausea...
AEs leading to
discontinuation/dose reduction:
Abdominal pain (grade 1-2, 1.8%)
Nausea (grade 1-3, 1.8%)
Sources: Page: p.1720
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Other AEs: Hair loss, Skin scaly...
Other AEs:
Hair loss
Skin scaly
Scales
Aphthous ulcer
Hematologic disorder
Sources:
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Other AEs: Epigastric discomfort, Vomiting...
AEs

AEs

AESignificanceDosePopulation
Vomiting 0.39%
Disc. AE
100 mg 2 times / day multiple, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Co-administed with::
chloroquine(155 mg; oral; 2/week)
Sources: Page: p.1891
healthy, 13–74
n = 511
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 13–74
Sex: M+F
Population Size: 511
Sources: Page: p.1891
Diarrhea 0.78%
Disc. AE
100 mg 2 times / day multiple, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Co-administed with::
chloroquine(155 mg; oral; 2/week)
Sources: Page: p.1891
healthy, 13–74
n = 511
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 13–74
Sex: M+F
Population Size: 511
Sources: Page: p.1891
Abdominal pain 0.98%
Disc. AE
100 mg 2 times / day multiple, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Co-administed with::
chloroquine(155 mg; oral; 2/week)
Sources: Page: p.1891
healthy, 13–74
n = 511
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 13–74
Sex: M+F
Population Size: 511
Sources: Page: p.1891
Nausea 1.17%
Disc. AE
100 mg 2 times / day multiple, oral
Recommended
Dose: 100 mg, 2 times / day
Route: oral
Route: multiple
Dose: 100 mg, 2 times / day
Co-administed with::
chloroquine(155 mg; oral; 2/week)
Sources: Page: p.1891
healthy, 13–74
n = 511
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 13–74
Sex: M+F
Population Size: 511
Sources: Page: p.1891
Headache 1.14%
Disc. AE
100 mg 1 times / day multiple, oral
Recommended
Dose: 100 mg, 1 times / day
Route: oral
Route: multiple
Dose: 100 mg, 1 times / day
Co-administed with::
atovaquone(250 mg oral; 1/day)
Sources: Page: p.745
healthy, 16 - 65
n = 175
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 16 - 65
Sex: M+F
Population Size: 175
Sources: Page: p.745
Abdominal pain grade 1-2, 1.8%
Disc. AE
150 mg 1 times / day multiple, oral (max)
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Co-administed with::
chloroquine(77.5-310 mg; oral; 1/week)
Sources: Page: p.1720
healthy, 3–16
n = 111
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 3–16
Sex: M+F
Population Size: 111
Sources: Page: p.1720
Nausea grade 1-3, 1.8%
Disc. AE
150 mg 1 times / day multiple, oral (max)
Recommended
Dose: 150 mg, 1 times / day
Route: oral
Route: multiple
Dose: 150 mg, 1 times / day
Co-administed with::
chloroquine(77.5-310 mg; oral; 1/week)
Sources: Page: p.1720
healthy, 3–16
n = 111
Health Status: healthy
Condition: malaria prophylaxis
Age Group: 3–16
Sex: M+F
Population Size: 111
Sources: Page: p.1720
Aphthous ulcer
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Hair loss
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Hematologic disorder
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Scales
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Skin scaly
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Epigastric discomfort
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Vomiting
200 mg 2 times / day multiple, oral (max)
Overdose
Dose: 200 mg, 2 times / day
Route: oral
Route: multiple
Dose: 200 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: P. falciparum malaria
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

Drug as victim
PubMed

PubMed

TitleDatePubMed
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs.
1990 Aug
Seizures after antimalarial medication in previously healthy persons.
2000 May-Jun
Application of higher throughput screening (HTS) inhibition assays to evaluate the interaction of antiparasitic drugs with cytochrome P450s.
2001 Jan
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Acute hepatitis and atovaquone/proguanil.
2005 Sep-Oct
Patents

Sample Use Guides

The daily dose should be taken at the same time each day with food or a milky drink. In the event of vomiting within 1 hour after dosing, a repeat dose should be taken. Prevention of Malaria: start prophylactic treatment with MALARONE (atovaquone and proguanil hydrochloride) 1 or 2 days before entering a malaria-endemic area and continue daily during the stay and for 7 days after return. Adults: One MALARONE Tablet (adult strength = 250 mg atovaquone/100 mg proguanil hydrochloride) per day. Pediatric Patients: The dosage for prevention of malaria in pediatric patients is based upon body weight. Treatment of Acute Malaria Adults: four malarone tablets (adult strength; total daily dose 1 g atovaquone/400 mg proguanil hydrochloride) as a single daily dose for 3 consecutive days. Pediatric Patients: The dosage for treatment of acute malaria in pediatric patients is based upon body weight.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: The in vitro effect of proguanil and its active metabolite cycloguanil on proliferating human blood mononuclear cells was studied. Proguanil had no effect on 14C-thymidine incorporation or on the number of cells. Cycloguanil, in concentrations corresponding to the plasma levels found in clinical practice, blocked the endogenous synthesis of thymidine and decreased the number of mitogen- and antigen-stimulated cells.
Unknown
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:02:51 UTC 2023
Edited
by admin
on Fri Dec 15 15:02:51 UTC 2023
Record UNII
ZT1D3VT2VU
Record Status Validated (UNII)
Record Version
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Name Type Language
PROGUANIL SULFATE
WHO-DD  
Common Name English
PROGUANIL SULPHATE
Common Name English
CHLOROGUANIDE SULFATE
Common Name English
Proguanil sulfate [WHO-DD]
Common Name English
CHLOROGUANIDE SULPHATE
Common Name English
Code System Code Type Description
PUBCHEM
71301233
Created by admin on Fri Dec 15 15:02:51 UTC 2023 , Edited by admin on Fri Dec 15 15:02:51 UTC 2023
PRIMARY
CAS
7586-61-0
Created by admin on Fri Dec 15 15:02:51 UTC 2023 , Edited by admin on Fri Dec 15 15:02:51 UTC 2023
PRIMARY
FDA UNII
ZT1D3VT2VU
Created by admin on Fri Dec 15 15:02:51 UTC 2023 , Edited by admin on Fri Dec 15 15:02:51 UTC 2023
PRIMARY
EPA CompTox
DTXSID70226770
Created by admin on Fri Dec 15 15:02:51 UTC 2023 , Edited by admin on Fri Dec 15 15:02:51 UTC 2023
PRIMARY
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ACTIVE MOIETY