Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H16F6N2O.ClH |
Molecular Weight | 414.773 |
Optical Activity | ( + ) |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.[H][C@@]1(CCCCN1)[C@@H](O)C2=C3C=CC=C(C3=NC(=C2)C(F)(F)F)C(F)(F)F
InChI
InChIKey=WESWYMRNZNDGBX-YLCXCWDSSA-N
InChI=1S/C17H16F6N2O.ClH/c18-16(19,20)11-5-3-4-9-10(15(26)12-6-1-2-7-24-12)8-13(17(21,22)23)25-14(9)11;/h3-5,8,12,15,24,26H,1-2,6-7H2;1H/t12-,15+;/m1./s1
Mefloquine, sold under the brand names Lariam among others, is a medication used to for the treatment of mild to moderate acute malaria caused by Mefloquineuine-susceptible strains of Plasmodium falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. Also for the prophylaxis of Plasmodium falciparum and Plasmodium vivax malaria infections, including prophylaxis of chloroquine-resistant strains of Plasmodium falciparum. Mefloquine acts as a blood schizonticide. Mefloquine is active against the erythrocytic stages of Plasmodium species. However, the drug has no effect against the exoerythrocytic (hepatic) stages of the parasite. Mefloquine is effective against malaria parasites resistant to chloroquine. Mefloquine is a chiral molecule. According to some research, the (+) enantiomer is more effective in treating malaria, and the (-) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.
CNS Activity
Curator's Comment: Male Wistar rats orally administered Mefloquine daily for 22 days at the equivalent human therapeutic plasma concentration showed CNS penetration of Mefloquine, with a 30 to 50 fold greater brain/plasma drug ratio up to 10 days after the final dose administered. The clinical use of mefloquine (MQ) has declined due to dose-related neurological events.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17404338
Curator's Comment: Mefloquine was developed by the United States Army in the 1970s. It is an antimalaria drug discovered by the US Army shortly after the Vietnam War, and subsequently marketed worldwide by F. Hoffmann-La Roche.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1440803 |
46.0 nM [EC50] | ||
Target ID: CHEMBL613897 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14967191 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | MEFLOQUINE HYDROCHLORIDE Approved UseTreatment of Acute Malaria Infections: Mefloquine hydrochloride tablets are indicated for the treatment of mild to moderate acute malaria caused by mefloquine-susceptible strains of P. falciparum (both chloroquine-susceptible and resistant strains) or by Plasmodium vivax. There are insufficient clinical data to document the effect of mefloquine in malaria caused by P. ovale or P. malariae. Note: Patients with acute P. vivax malaria, treated with mefloquine, are at high risk of relapse because mefloquine does not eliminate exoerythrocytic (hepatic phase) parasites. To avoid relapse, after initial treatment of the acute infection with mefloquine, patients should subsequently be treated with an 8-aminoquinoline derivative (e.g., primaquine).
Prevention of Malaria: Mefloquine hydrochloride tablets are indicated for the prophylaxis of P. falciparum and P. vivax malaria infections, including prophylaxis of chloroquine-resistant strains of P. falciparum. Launch Date1989 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1018 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148 |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEFLOQUINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
432 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148 |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEFLOQUINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
396 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9860148 |
750 mg single, oral dose: 750 mg route of administration: Oral experiment type: SINGLE co-administered: |
MEFLOQUINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
MEFLOQUINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
25 mg/kg single, oral Highest studied dose Dose: 25 mg/kg Route: oral Route: single Dose: 25 mg/kg Sources: Page: p.836 |
unhealthy, 0.4-88 n = 873 Health Status: unhealthy Condition: Acute falciparum malaria Age Group: 0.4-88 Sex: M+F Population Size: 873 Sources: Page: p.836 |
|
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Halofantrine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: Page: p.12 |
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Ketoconazole Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Other AEs: Electrocardiogram QTc interval prolonged... Other AEs: Electrocardiogram QTc interval prolonged Sources: Page: p.12 |
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: chloroquine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Disc. AE: Electrocardiogram abnormal... AEs leading to discontinuation/dose reduction: Electrocardiogram abnormal Sources: Page: p.12 |
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: quinine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Disc. AE: Electrocardiogram abnormal... AEs leading to discontinuation/dose reduction: Electrocardiogram abnormal Sources: Page: p.12 |
1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Disc. AE: Anxiety, Paranoia... AEs leading to discontinuation/dose reduction: Anxiety Sources: Page: p.12Paranoia Depression Hallucinations Psychotic behavior |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Electrocardiogram QTc interval prolonged | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Halofantrine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
|
Electrocardiogram QTc interval prolonged | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: Ketoconazole Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
|
Electrocardiogram abnormal | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: chloroquine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Electrocardiogram abnormal | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Co-administed with:: quinine Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Anxiety | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Depression | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Hallucinations | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Paranoia | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Psychotic behavior | Disc. AE | 1250 mg single, oral Recommended Dose: 1250 mg Route: oral Route: single Dose: 1250 mg Sources: Page: p.12 |
unhealthy Health Status: unhealthy Condition: Malaria Sources: Page: p.12 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://aac.asm.org/content/59/1/96 |
no | |||
Sources: https://aac.asm.org/content/59/1/96 |
no | |||
Sources: https://aac.asm.org/content/59/1/96 |
no | |||
yes [IC50 21 uM] | ||||
yes [IC50 27 uM] | ||||
Sources: https://aac.asm.org/content/59/1/96 |
yes | |||
Sources: https://aac.asm.org/content/59/1/96 |
yes | |||
Sources: https://aac.asm.org/content/59/1/96 |
yes | |||
Sources: https://aac.asm.org/content/59/1/96 |
yes | |||
Sources: https://aac.asm.org/content/59/1/96 |
yes | |||
Sources: https://aac.asm.org/content/59/1/96 |
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 7.0 |
yes | |||
Page: 2.0 |
yes | yes (co-administration study) Comment: Co-administration of a single 500 mg oral dose of Lariam with 400 mg of ketoconazole once daily for 10 days in 8 healthy volunteers resulted in an increase in the mean Cmax and AUC of mefloquine by 64% and 79%, respectively, and an increase in the mean elimination half-life of mefloquine from 322 hours to 448 hours. Page: 2.0 |
Sample Use Guides
Treatment of mild to moderate malaria in adults caused by mefloquine-susceptible strains of P. falciparum or by P. vivax: Dosage: Five tablets (1250 mg) mefloquine hydrochloride to be given as a single oral dose. The drug should not be taken on an empty stomach and should be administered with at least 8 oz (240 mL) of water. The recommended prophylactic dose of mefloquine is approximately 5 mg/kg body weight once weekly. One 250 mg mefloquine hydrochloride tablet should be taken once weekly in pediatric patients weighing over 45 kg.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1440803
Mefloquine inhibited chloroquine-resistant strains of Plasmodium falciparum in vitro. The EC50 values for mefloquine were 46-185 nM. At higher concentrations, strains K1 and LS21 were fully inhibited, while with strain T996 mefloquine did not fully inhibit even at the highest concentration, 1.28 x 10(-6) M.
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SUBSTANCE RECORD