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Details

Stereochemistry ACHIRAL
Molecular Formula C11H16ClN5
Molecular Weight 253.731
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROGUANIL

SMILES

CC(C)NC(=N)NC(=N)NC1=CC=C(Cl)C=C1

InChI

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

HIDE SMILES / InChI

Description

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.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
MALARONE
Preventing
MALARONE

Cmax

ValueDoseCo-administeredAnalytePopulation
39 ng/mL
3.5 mg/kg bw single, oral
(4-CHLOROPHENYL)BIGUANIDE blood
Homo sapiens
10 ng/mL
3.5 mg/kg bw single, oral
(4-CHLOROPHENYL)BIGUANIDE plasma
Homo sapiens
980 ng/mL
3.5 mg/kg bw single, oral
PROGUANIL blood
Homo sapiens
170 ng/mL
3.5 mg/kg bw single, oral
PROGUANIL plasma
Homo sapiens
190 ng/mL
200 mg 1 times / day steady-state, oral
PROGUANIL plasma
Homo sapiens
209 ng/mL
200 mg single, oral
PROGUANIL plasma
Homo sapiens
50 ng/mL
3.5 mg/kg bw single, oral
CYCLOGUANIL blood
Homo sapiens
41 ng/mL
3.5 mg/kg bw single, oral
CYCLOGUANIL plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
883 ng × h/mL
3.5 mg/kg bw single, oral
(4-CHLOROPHENYL)BIGUANIDE blood
Homo sapiens
249 ng × h/mL
3.5 mg/kg bw single, oral
(4-CHLOROPHENYL)BIGUANIDE plasma
Homo sapiens
14070 ng × h/mL
3.5 mg/kg bw single, oral
PROGUANIL blood
Homo sapiens
2975 ng × h/mL
3.5 mg/kg bw single, oral
PROGUANIL plasma
Homo sapiens
141 μg × min/mL
200 mg single, oral
CYCLOGUANIL plasma
Homo sapiens
834 ng × h/mL
3.5 mg/kg bw single, oral
CYCLOGUANIL blood
Homo sapiens
190 μg × min/mL
200 mg 1 times / day steady-state, oral
CYCLOGUANIL plasma
Homo sapiens
661 ng × h/mL
3.5 mg/kg bw single, oral
CYCLOGUANIL plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
15.7 h
3.5 mg/kg bw single, oral
PROGUANIL blood
Homo sapiens
16.1 h
3.5 mg/kg bw single, oral
PROGUANIL plasma
Homo sapiens
21 h
200 mg 1 times / day steady-state, oral
PROGUANIL plasma
Homo sapiens
18 h
200 mg single, oral
PROGUANIL plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as victim

PubMed

Sample Use Guides

In Vivo Use Guide
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
Unknown