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HALOFANTRINE

Pharmacology and mechanism of action Indications Side effects Contraindications and precautions Interactions Preparations References
HALOFANTRINE
HALOFANTRINE structure
CAS No.
69756-53-2
Chemical Name:
HALOFANTRINE
Synonyms
Halofan;WR-171669;SKF-102886;HALOFANTRINE;3-(Dibutylamino)-1-(1,3-dichloro-6-(trifluoromethyl)-phenanthren-9-yl)propan-1-ol;1,3-Dichloro-α-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9-phenanthrenemethanol;3-DIBUTYLAMINO-1-(1,3-DICHLORO-6-TRIFLUOROMETHYL-PHENANTHREN-9-YL)-PROPAN-1-OL HCL;9-Phenanthrenemethanol,1,3-dichloro-a-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-;1,3-Dichloro-alpha-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9-phenanthrenemethanol;9-Phenanthrenemethanol, 1,3-dichloro-.alpha.-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-
CBNumber:
CB6377605
Molecular Formula:
C26H30Cl2F3NO
Formula Weight:
500.42
MOL File:
69756-53-2.mol

HALOFANTRINE Properties

Density 
1.244±0.06 g/cm3 (20 ºC 760 Torr)

SAFETY

HALOFANTRINE price

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HALOFANTRINE Chemical Properties,Uses,Production

Pharmacology and mechanism of action

Halofantrine is a phenanthrenemethanol antimalarial drug developed by the US military. The antimalarial activity of the phenanthrenemethanols was discovered during the Second World War but was not exploited until later. Halofantrine is a potent blood schizontocide against Plasmodium falciparum both in vitro and in vivo. However, it has no effect against exoerythrocytic forms of the parasite. Experience of its activity against other malaria species is limited. The drug exists as a racemic mixture, but the two enantiomers have shown similar activity in vitro [1, 2].
The mechanism of action of halofantrine is not known.

Indications

Halofantrine is indicated only for the treatment of multidrug-resistant Plasmodium falciparum malaria.

Side effects

Halofantrine is generally well tolerated. Mild and transient side effects such as nausea, vomiting, diarrhoea, abdominal pain, pruritus and rash have been reported in humans. Halofantrine is potentially cardiotoxic particularly with doses above the recommended dose and causes ECG changes such as prolongation of PR and QTc intervals. In one study, the sudden death of a patient was reported after receiving a high dose of halofantrine (8 mg/kg 3 times daily for 3 days) [3]. The patient had previously been treated with mefloquine. Cardiotoxicity due to halofantrine will become a therapeutic problem if higher dosage regimens have to be used due to decreased efficacy [3]. Occasional elevation of serum transaminase have been observed in some patients. The relationship of this to the treatment is unclear. Values usually return to normal levels within a week after treatment [4-6].

Contraindications and precautions

Halofantrine should not be given to patients with pre-existing cardiovascular diseases. There is a warning against the concomitant intake of any cardiotoxic drugs. Halofantrine is not used for malaria prophylaxis.

Interactions

There are no reports of interactions [7].

Preparations

Available as halofantrine hydrochloride: 100 mg hydrochloride is equal to 93 mg base. Not yet available for parenteral use.
• Halfan® (SmithKline & Beecham). Tablets 250 mg. Oral suspension 20 mg/ml.

References

1. Bryson HM, Goa KL (1992). Halofantrine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic potential. Drugs, 43, 236–258.
2. Karle JM, Olmeda R, Gerena L, Milhous WK (1994). Plasmodium falciparum: Role of absolute stereochemistry in the antimalarial activity of synthetic aminoalcohol antimalarial agents. Exp Parasitol, 76, 345–351.
3. Nosten F, ter Kuile FO, Luxemburger C, Woodrow C, Kyle DPE, Chongsuphajaisiddhi T, White NJ (1993). Cardiac effects of antimalarial treatment with halofantrine. Lancet, 341, 1054–1056.
4. Watkins WM, Lury JD, Kariuki D, Koech DK, Oloo JA, Mosoba M, Mjomba M, Gilles HM (1988). Efficacy of multiple-dose halofantrine in treatment of chloroquine-resistant falciparum malaria in children in Kenya. Lancet, 2, 247–250.
5. Salako LA, Sowunmi A, Walker O (1990). Evaluation of the Clinical trials and safety of halofantrine in falciparum malaria in Ibadan Nigeria. Trans R Soc Trop Med Hyg, 84, 644–647.
6. Boudreau EF, Pang LW, Dixon KE, Webster HK, Pavanand K, Tosingha L, Somutsakorn P, Canfield CJ (1988). Malaria: Treatment efficacy of halofantrine (WR171,669) in initial field trials in
7. Karbwang J, Na Bangchang K (1994). Clinical pharmacokinetics of halofantrine. Clin Pharmacokinet, 27(2), 104–119.

Description

Halofantrine is an orally-active blood schizonticide reportedly highly effective in the treatment of fulcipurum malaria and other types of parasitemia. Cure rate is claimed to be over 95%.

Originator

Smith mine & French (USA)

brand name

Halfan

World Health Organization (WHO)

Halofantrine is an antimalarial introduced to medicine in 1982. It should be reserved for use in areas where multiple drug-resistant falciparum malaria is prevalent. Cases of serious cardiotoxicity have been reported.

Antimicrobial activity

It inhibits erythrocytic stages of chloroquine-sensitive and chloroquine-resistant P. falciparum and other Plasmodium spp. in vitro at concentrations of 0.4–4.0 mg/L. It is more active than mefloquine and the combination of proguanil and atovaquone against P. falciparum, but less effective than mefloquine or chloroquine against P. vivax.

Acquired resistance

Resistance in P. falciparum has been reported in Central and West Africa, where it has been used widely. Cross-resistance with mefloquine has been reported in Thailand, where it has not been used.

General Description

Structurally, halofantrine differs from allother antimalarial drugs. It is a good example of drug designthat incorporates bioisosteric principles as evidenced by thetrifluromethyl moiety. Halofantrine is a schizonticide and has no affect on the sporozoite, gametocyte,or hepatic stages. Both the parent compound and Ndesbutylmetabolite are equally active in vitro. Halfantrine’sspecific mechanism of action against the parasite is notknown. There is contradictory evidence that its mechanismranges from requiring heme to disrupting the mitochondria.There is a prominent warning that halfantrine can affectnerve conduction in cardiac tissue.

Pharmaceutical Applications

A phenanthrene methanol, formulated as the hydrochloride for oral administration. Parenteral formulations are not available. The enantiomers have equivalent activity in vitro. Aqueous solubility is extremely low.

Pharmacokinetics

Absorption shows high intra- and inter-subject variability and depends on co-administration with fats. Bioavailability is increased more than six-fold after a fatty meal or by lipidbased formulations. Bioavailability is significantly lower in patients with malaria than in healthy individuals. Peak plasma levels are variable and occur 3–6 h after administration. Unlike many other antimalarials, halofantrine is not concentrated by infected or uninfected erythrocytes. Distribution to lipoproteins is stereo-selective. About 20–30% of the dose is metabolized to an N-desbutyl derivative by cytochrome P450 (CYP) 3A4 and 3A5. The elimination half-life of the parent drug is generally 1–2 days and that of the metabolite 3 days. Little unchanged drug is excreted in urine.

Clinical Use

Treatment of multidrug-resistant falciparum malaria
Its use has been questioned due to the existence of safer alternatives.

Side effects

Abdominal pain, diarrhea and pruritus are the most frequent. High doses (24 mg/kg) induce prolongation of the PR and QTc intervals; this is not stereo-selective. There are individual reports of fatal cardiac arrest and torsade de pointes. To reduce the risk of cardiac toxicity it should be taken on an empty stomach. It should not be administered with other antimalarials that have the potency to induce cardiac arrhythmias (mefloquine, chloroquine, quinine). Halofantrine has also been associated with intravascular hemolysis.

HALOFANTRINE Preparation Products And Raw materials

Raw materials

Preparation Products


HALOFANTRINE Suppliers

Global( 39)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
3B Pharmachem (Wuhan) International Co.,Ltd. 86-21-50328103 * 801、802、803、804 Mobile:18930552037
86-21-50328109 3bsc@sina.com China 15884 69
Pure Chemistry Scientific Inc. 001-857-928-2050 or 1-888-588-9418
001-617-206-9595 sales@chemreagents.com United States 9922 62
LGM Pharma 1-(800)-881-8210
615-250-9817 inquiries@lgmpharma.com United States 1943 70
Shanghai Fuhe Chemistry Technology Co., Ltd. 0086-21-67651709
0086-21-67651705 cfx759@hotmail.com China 410 57
Wuhan Haizheng Industry & Trade Development Co. Ltd 027-8866 0053/88660577/88660578
027-8899 1911 pb@whhz.cn China 1082 55
T&W GROUP +86-21-61551611, 61551462, 61551420, 61551610
+86-21-50676805 contact@trustwe.com China 10519 58
Beijing HuaMeiHuLiBiological Chemical 010-56205725;010-86181995
010-65763397 waley188@sohu.com China 12343 58
Hangzhou J&H Chemical Co., Ltd. +86-0571-87396432
+86-0571-87396431 sales@jhechem.com China 13902 53
parabiochem 025-83453382-8005
025-83453382 sale@parabiochem.com China 9617 55
Wuhan Wsem Biological Co., Ltd. 027-59402396 ; 13419635609(WX)
027-59402396 13419635609@163.com China 4573 55

69756-53-2(HALOFANTRINE)Related Search:


  • HALOFANTRINE
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  • 1,3-Dichloro-α-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9-phenanthrenemethanol
  • Halofan
  • SKF-102886
  • WR-171669
  • 9-Phenanthrenemethanol, 1,3-dichloro-.alpha.-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-
  • 1,3-Dichloro-alpha-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9-phenanthrenemethanol
  • 3-(Dibutylamino)-1-(1,3-dichloro-6-(trifluoromethyl)-phenanthren-9-yl)propan-1-ol
  • 9-Phenanthrenemethanol,1,3-dichloro-a-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-
  • 69756-53-2
  • C26H30Cl2F3NO
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