HALOFANTRINE CAS 69756-53-2
Introduction：Basic information about HALOFANTRINE CAS 69756-53-2, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
HALOFANTRINE Basic informationPharmacology and mechanism of action Indications Side effects Contraindications and precautions Interactions Preparations References
| Product Name: | HALOFANTRINE |
| Synonyms: | HALOFANTRINE;3-DIBUTYLAMINO-1-(1,3-DICHLORO-6-TRIFLUOROMETHYL-PHENANTHREN-9-YL)-PROPAN-1-OL HCL;Halofan;SKF-102886;WR-171669;1，3-Dichloro-α-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9-phenanthrenemethanol;9-Phenanthrenemethanol, 1,3-dichloro-.alpha.-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-;9-Phenanthrenemethanol,1,3-dichloro-a-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)- |
| CAS: | 69756-53-2 |
| MF: | C26H30Cl2F3NO |
| MW: | 500.42 |
| EINECS: | 274-104-1 |
| Product Categories: | |
| Mol File: | 69756-53-2.mol |
HALOFANTRINE Chemical Properties
| density | 1.244±0.06 g/cm3 (20 ºC 760 Torr) |
| storage temp. | 2-8°C |
| Water Solubility | 0.59mg/L(37 ºC) |
Safety Information
| 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 thetreatment of fulcipurum malaria and other types of parasitemia. Cure rate is claimed to beover 95%. |
| Originator | Smith mine & French (USA) |
| Definition | ChEBI: 3-(dibutylamino)-1-[1,3-dichloro-6-(trifluoromethyl)-9-phenanthrenyl]-1-propanol is a member of phenanthrenes. |
| Brand name | Halfan |
| World Health Organization (WHO) | Halofantrine is an antimalarial introduced to medicine in 1982. Itshould be reserved for use in areas where multiple drug-resistant falciparummalaria is prevalent. Cases of serious cardiotoxicity have been reported. |
| Antimicrobial activity | It inhibits erythrocytic stages of chloroquine-sensitive andchloroquine-resistant P. falciparum and other Plasmodium spp.in vitro at concentrations of 0.4–4.0 mg/L. It is more activethan mefloquine and the combination of proguanil and atovaquoneagainst P. falciparum, but less effective than mefloquineor chloroquine against P. vivax. |
| Acquired resistance | Resistance in P. falciparum has been reported in Central andWest Africa, where it has been used widely. Cross-resistancewith mefloquine has been reported in Thailand, where it hasnot 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 hydrochloridefor oral administration. Parenteral formulations are notavailable. The enantiomers have equivalent activity in vitro.Aqueous solubility is extremely low. |
| Pharmacokinetics | Absorption shows high intra- and inter-subject variabilityand depends on co-administration with fats. Bioavailability isincreased more than six-fold after a fatty meal or by lipidbasedformulations. Bioavailability is significantly lower inpatients with malaria than in healthy individuals. Peak plasmalevels are variable and occur 3–6 h after administration.Unlike many other antimalarials, halofantrine is not concentratedby infected or uninfected erythrocytes. Distribution tolipoproteins is stereo-selective. About 20–30% of the dose ismetabolized to an N-desbutyl derivative by cytochrome P450(CYP) 3A4 and 3A5. The elimination half-life of the parentdrug 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 saferalternatives. |
| Side effects | Abdominal pain, diarrhea and pruritus are the most frequent.High doses (24 mg/kg) induce prolongation of the PR andQTc intervals; this is not stereo-selective. There are individualreports of fatal cardiac arrest and torsade de pointes.To reduce the risk of cardiac toxicity it should be taken onan empty stomach. It should not be administered with otherantimalarials that have the potency to induce cardiac arrhythmias(mefloquine, chloroquine, quinine). Halofantrine hasalso been associated with intravascular hemolysis. |
| Metabolism | Halofantrine is considered to be an alternative drug for treatment of both chloroquine-sensitiveand chloroquine-resistant Plasmodium falci parum malaria, but its efficacy in mefloquine-resistantmalaria may be questionable. The drug is metabolized via N-dealkylation to desbutylhalofantrineby CYP3A4. The metabolite appears to be several-fold more active than theadministered drug. |
HALOFANTRINE Preparation Products And Raw materials
| Raw materials | 1-Bromobutane-->Phenanthrene-->Diborane |
