Halofantrine hydrochloride (SKF-102886)
(Synonyms: 盐酸卤泛群,SKF-102886; WR-171669 hydrochloride) 目录号 : GC32377An antimalarial agent
Cas No.:36167-63-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Halofantrine is an antimalarial agent.1 It is active against chloroquine-sensitive and chloroquine-resistant strains of P. falciparum (IC50s = 1.5-2.5 and 1.3-3.9 ?g/L, respectively). Halofantrine reduces parasitemia in a mouse model of P. berghei infection with a 50% curative dose (CD50) value of 15 mg/kg. It also reduces parasitemia in an Aotus monkey model of P. falciparum infection (CD50 = 58.3 mg/kg). Formulations containing halofantrine have been used in the treatment of malaria.
1.Bryson, H., and Goa, K.L.Halofantrine. A review of its antimalarial activity, pharmacokinetic properties and therapeutic potentialDrugs43(2)236-258(1992)
| Cas No. | 36167-63-2 | SDF | |
| 别名 | 盐酸卤泛群,SKF-102886; WR-171669 hydrochloride | ||
| Canonical SMILES | OC(CCN(CCCC)CCCC)C1=CC2=C(Cl)C=C(Cl)C=C2C3=CC(C(F)(F)F)=CC=C31.[H]Cl | ||
| 分子式 | C26H31Cl3F3NO | 分子量 | 536.88 |
| 溶解度 | DMSO : 30 mg/mL (55.88 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8626 mL | 9.3131 mL | 18.6261 mL |
| 5 mM | 0.3725 mL | 1.8626 mL | 3.7252 mL |
| 10 mM | 0.1863 mL | 0.9313 mL | 1.8626 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Halofantrine hydrochloride--efficacy and safety in children with acute malaria
J Pak Med Assoc 1991 Jan;41(1):8-10.PMID:1900550doi
Thirty two children with symptomatic malaria due to P. vivax and P. Falciparum infections were treated with three doses of Halofantrine hydrochloride 8 mg/kg body weight every 6 hours. Mean fever clearance was 30 hours (range 24-48 hours). No significant clinical or biochemical side effects were observed. Symptoms cleared rapidly. Halofantrine hydrochloride was found to be highly effective and appeared to have no side effects in children with acute malaria infections.
Structure of the antimalarial Halofantrine hydrochloride
Acta Crystallogr C 1989 Aug 15;45 ( Pt 8):1248-50.PMID:2604946DOI:10.1107/s0108270189002210.
1,3-Dichloro-alpha-[2-(dibutylamino)ethyl]-6-(trifluoromethyl)-9- phenanthrenemethanol hydrochloride, C26H31Cl2F3NO+.Cl-, Mr = 536.9, monoclinic, P21/n, alpha = 8.169 (3), b = 32.924 (13), c = 22.775 (6) A, beta = 98.99 (3) degrees, V = 6050.2 A3, Z = 8, Dx = 1.18 g cm-3, Cu K alpha, lambda = 1.54178 A, mu = 15.51 cm-1, F(000) = 2240, room temperature, final R = 18.3% for 2899 reflections with [Fo] greater than 3 sigma. The crystal structure of Halofantrine hydrochloride was determined to 1.0 to 1.1 A resolution. The high R factor is due to poor crystal quality. In order to have a crystal with sufficient thickness for data collection, it was necessary to use a crystal that had grown in layers. The high R factor is also due to a disordered CF3 group, a disordered solvent channel, and high thermal factors on the long hydrocarbon chains. The two halofantrine conformers stack such that the phenanthrene rings are nearly on top of each other with the chlorine and CF3 groups on opposite sides and with the hydrocarbon side chains projected away from each other, but on the same side of the phenanthrene rings. Atoms in the phenanthrene rings of the two stacked conformers are separated by 3.4 to 3.7 A. On each of the halofantrine conformers, one of the n-butyl groups extends in a linear fashion whereas the other n-butyl group is bent back towards the phenanthrene ring.(ABSTRACT TRUNCATED AT 250 WORDS)
Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation
Br J Clin Pharmacol 2001 Mar;51(3):231-7.PMID:11298069DOI:10.1046/j.1365-2125.2001.00351.x.
Aims: 1) To characterize the variability of multiple-dose halofantrine pharmacokinetics over time in healthy adults, 2) to correlate the pharmacodynamic measure electrocardiographic (ECG) QT interval with (+)- and (-)-halofantrine plasma concentration and 3) to evaluate the safety and tolerance of Halofantrine hydrochloride given over time to healthy adults. Methods: Twenty-one healthy subjects were enrolled and 13 completed the study (180 days). Subjects received either 500 mg of racemic halofantrine once daily in the fasted state for 42 days, or placebo, and then halofantrine washout was documented for the following 138 days. Pharmacokinetic and pharmacodynamic (ECG QTc) measurements were obtained. Results: Mean accumulation half-times (days) for halofantrine were: 7.0 +/- 4.8 [(+)-halofantrine] and 7.3 +/- 4.8 [(-)-halofantrine]. Mean steady-state concentrations were: 97.6 +/- 52.0 ng ml(-1) [(+)-halofantrine] and 48.5 +/- 20.8 [(-)-halofantrine]. Steady-state oral clearance was: 139 +/- 73 l h(-1) [(+)-halofantrine] and 265 +/- 135 l h(-1) [(-)-halofantrine]. Peak plasma concentrations of both (+)- and (-)-halofantrine were attained at 6 h and maximal ECG QTc prolongation was at 4-8 h following drug administration. Fourteen of 16 subjects who received active drug had ECG QTc prolongation that was positively correlated with both (+)- and (-)-halofantrine concentration. The five subjects who received placebo had no demonstrable change in ECG QTc throughout the study. Conclusions Halofantrine accumulates extensively and shows high intersubject pharmacokinetic variability, is associated with concentration-related ECG QTc prolongation in healthy subjects, and is clinically well tolerated in this subject group.
Partitioning of Halofantrine hydrochloride between water, micellar solutions, and soybean oil: Effects on its apparent ionization constant
J Pharm Sci 2003 Nov;92(11):2217-28.PMID:14603507DOI:10.1002/jps.10479.
Recent studies in a conscious dog model demonstrated intestinal lymphatic transport to be a significant contributor to the bioavailability of the highly lipid-soluble free-base of halofantrine (Hf), and surprisingly, also the poorly lipid-soluble hydrochloride salt (Hf. HCl). Partial conversion of solubilized Hf. HCl to Hf base within the intestinal lumen prior to the lymphatic uptake seemed to be the most likely explanation for these results. This hypothesis was supported by studies exploring the partitioning behavior of Hf. HCl between soybean oil (SBO) and aqueous micellar solutions containing different ionic and nonionic surfactants. Mixed micelles prepared from sodium taurodeoxycholate (NaTC) and lecithin (PC) were chosen to represent fed-state intestinal fluids. The apparent ionization constants derived from the partitioning versus pH profiles showed marked shifts when compared with the likely aqueous pK(a) value. In the present paper, the apparent pK(a) values of Hf in aqueous micellar phases, without a coexisting oil phase, were investigated to further probe the mechanisms underlying the effect of micellar media on the apparent ionization equilibrium, and subsequently, on its partitioning behavior in the triphasic systems. Another aim of this study was to further evaluate the aqueous pK(a) value of Hf. The results indicate that the aqueous pK(a) of Hf is most probably in the range approximately 8-9, and that the ionization equilibrium is highly dependent on the solution environment. For example, marked pK(a) shifts of several units were observed for Hf in the presence of different micellar species and SBO. The apparent ionization equilibrium depends not only on interaction of Hf with the micelles, but also on its partitioning into the oil phase.
Effect of fluconazole on the pharmacokinetics of halofantrine in healthy volunteers
J Clin Pharm Ther 2009 Dec;34(6):677-82.PMID:20175801DOI:10.1111/j.1365-2710.2009.01064.x.
Background: Halofantrine, an antimalarial drug used in endemic areas such as the tropics is mainly metabolized by CYP3A4 to the active metabolite N-desbutylhalofantrine. Fluconazole, an antifungal agent and an inhibitor of CYP3A4 is an established part of the therapy in HIV patients, who in turn are prone to malaria in the tropics. This study investigated the effect of fluconazole on the pharmacokinetics of halofantrine after concurrent administration of the two drugs. Methods: The effect of fluconazole on the pharmacokinetics of the antimalarial drug halofantrine was evaluated in 15 healthy volunteers in a Latin Square crossover design. The subjects received a single oral dose of 500 mg Halofantrine hydrochloride alone or with 50 mg fluconazole after an overnight fast. Venous blood samples were collected during the next 336 h and analysed by HPLC for halofantrine and its active metabolite N-desbutylhalofantrine. Results: Co-administration of fluconazole did not alter the pharmacokinetics of halofantrine significantly with the exception of elimination t(1/2) that was significantly increased by 25% (P < 0.05). In contrast, fluconazole significantly altered the pharmacokinetic parameters of the active metabolite by reducing C(max), AUC and metabolite ratio (N-desbutylhalofantrine/halofantrine) between 35 and 41% (P < 0.05) while increasing t(max) by 50%. The 90% confidence intervals of the ratio of the geometric means (with/without fluconazole) were contained within 80-125% for halofantrine but outside this range for N-desbutylhalofantrine. Conclusion: The decreased plasma concentrations of the metabolite are presumably caused by metabolic inhibition of CYP3A4 by fluconazole. Although the therapeutic consequences of this interaction are not clear caution should be exercised when co-administering both drugs to avoid accumulation and subsequent cardiotoxic effects of halofantrine.