Details
Stereochemistry | RACEMIC |
Molecular Formula | C26H30Cl2F3NO.ClH |
Molecular Weight | 536.885 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CCCCN(CCCC)CCC(O)C1=C2C=CC(=CC2=C3C=C(Cl)C=C(Cl)C3=C1)C(F)(F)F
InChI
InChIKey=WANGFTDWOFGECH-UHFFFAOYSA-N
InChI=1S/C26H30Cl2F3NO.ClH/c1-3-5-10-32(11-6-4-2)12-9-25(33)23-16-22-21(14-18(27)15-24(22)28)20-13-17(26(29,30)31)7-8-19(20)23;/h7-8,13-16,25,33H,3-6,9-12H2,1-2H3;1H
DescriptionCurator's Comment: Description was created using several sources including:
https://www.sri.com/newsroom/press-releases/sri-international-celebrates-50-years-drug-discovery-and-development-contrib;
http://www.drugbank.ca/drugs/DB01218
Curator's Comment: Description was created using several sources including:
https://www.sri.com/newsroom/press-releases/sri-international-celebrates-50-years-drug-discovery-and-development-contrib;
http://www.drugbank.ca/drugs/DB01218
Halofantrine is a blood schizonticidal antimalarial agent with no apparent action on the sporozoite, gametocyte or hepatic stages of the infection. It is used only to treat but not to prevent malaria. Has been marketed by GlaxoSmithKline as HALFAN (halofantrine hydrochloride) in 250 mg tablets indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax. Among side effects is cardiac arrhythmia. It belongs to the phenanthrene class of compounds that includes quinine and lumefantrine. It was reported that halofantrine binds to hematin in vitro (crystal structure of the complex) and to to plasmpesin, a haemoglobin degrading enzyme unique to the malarial parasites.
Originator
Curator's Comment: In the 1970s, SRI developed halofantrine for the U.S. Army as a treatment for drug-resistant malaria. It was distributed by the World Health Organization (WHO). It was approved by FDA as an antimalarial in 1992 under the SmithKline Beecham (now GlaxoSmithKline) brand name, Halfan®.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18508124 |
0.79 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | HALFAN Approved UseHalfan tablets are indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax. Launch Date1993 |
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Curative | HALFAN Approved UseHalfan tablets are indicated for the treatment of adults who can tolerate oral medication and who have mild to moderate malaria (equal to or less than 100,000 parasites/mm3) caused by Plasmodium falciparum or Plasmodium vivax. Launch Date1992 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
114 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
191 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
79 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1218 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
185 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
345 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
546 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
3200 ng/mL |
500 mg 3 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
17.33 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
24.46 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
8.76 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESBUTYLHALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
11.3 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: HIGH-FAT |
|
3.92 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
7.86 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
9.36 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
81 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
98 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
72 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2775616/ |
1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
8 day |
500 mg 3 times / day multiple, oral dose: 500 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
HALOFANTRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FED |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Disc. AE: Vomiting of medication, Consciousness decreased... Other AEs: Convulsions, Stomatitis... AEs leading to discontinuation/dose reduction: Vomiting of medication (3 patients) Other AEs:Consciousness decreased (2 patients) Convulsions (3 patients) Sources: Page: 7Stomatitis (3 patients) Pulmonary edema (1 patient) Tetany (1 patient) Hypertensive crisis (1 patient) Cerebrovascular accident (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Cerebrovascular accident | 1 patient | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Hypertensive crisis | 1 patient | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Pulmonary edema | 1 patient | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Tetany | 1 patient | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Consciousness decreased | 2 patients Disc. AE |
500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Convulsions | 3 patients | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Stomatitis | 3 patients | 500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Vomiting of medication | 3 patients Disc. AE |
500 mg 3 times / day single, oral Recommended Dose: 500 mg, 3 times / day Route: oral Route: single Dose: 500 mg, 3 times / day Sources: Page: 7 |
unhealthy, adult n = 933 Health Status: unhealthy Condition: malaria Age Group: adult Sex: unknown Population Size: 933 Sources: Page: 7 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 1.06 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | yes (co-administration study) Comment: grapefruit juice increased halofantrine area under the plasma concentration versus time curve (AUC) and peak plasma concentration by 2.8-fold Sources: https://pubmed.ncbi.nlm.nih.gov/10385214/ |
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minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
minor | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
In vitro cultivation of Cryptosporidium parvum and screening for anticryptosporidial drugs. | 1990 Aug |
|
A new high-performance liquid chromatography (HPLC) method for the analysis of halofantrine (HF) in pharmaceuticals. | 2002 Jul 31 |
|
In vitro susceptibility of Plasmodium falciparum to monodesethylamodiaquine, quinine, mefloquine and halofantrine in Abidjan (Côte d'Ivoire). | 2010 Jun |
Sample Use Guides
The recommended treatment consists of 2 courses of 1500 mg. One course dosage is 500 mg (2 x 250 mg tablets) given every 6 hours for 3 doses, repeated in 7 days. Halofantrine is administered at least 1 hour before or 2 hours after food.
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/3885770
Antimalarial activity of halofantrine against 33 strains of P. falciparum isolated from naturally acquired malaria infections in Thailand was determined using a radioisotope microdilution method. 0.2-25 ng/ml of halofantrine was added to test isolates of P. falciparum. Susceptibility response ID50 was 0.63-0.73 ng/ml.
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CHEMBL1107
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DBSALT001186
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SUB02451MIG
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58130
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100000088512
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m5900
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37392
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C65839
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252-895-4
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H77DL0Y630
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DTXSID0045464
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106927-11-1
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36167-63-2
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ACTIVE MOIETY
SUBSTANCE RECORD