Diloxanide furoate

E. histolytica colonization of the large intestine is eradicated using a luminal agent such as diloxanid furoate or paromomycin. Invasive amoebiasis (colitis,... 

C3,H9Cl2N02 579-38-4) see Diloxanide furoate 6,8-dimercaptooctanoic acid methyl ester 6-acetate 8-sulfate sodium salt... 

C4H4O4 110-17-8) see Biotin Ibutilide fumarate Quetiapine fumarate Sodium dioctyl sulfosuccinate furan-2-carbonyl chloride (CjHjClOj 527-69-5) see Diloxanide furoate Mometasone furoate Terazosin 2(5ff)-furanone... 

The pediatric dose of paromomycin is the same as that used in adults, whereas the pediatric dose of iodoquinol is 30 to 40 mg/kg (maximum 2 g) per day in three doses for 20 days, and the pediatric dose of diloxanide furoate is 20 mg/kg per day in three doses for 10 days. Paromomycin is the preferred agent in pregnant patients.3... 

Diloxanide Furoate 0.3 g Potentiometric determination Each ml of 0.1 N Tetrabutylammonium hydroxide = 0.03282 g of C14HnCl2N04... 

Of the dichloroacetamides diloxanide furoate, clefamide, teclozan and etofamide the most frequently used agent is diloxanide furoate. It is the luminal amoebicide of choice in chronic intestinal amoebiasis, however it lacks efficacy acute intestinal amoebiasis. Its mechanism of action is unknown. Given orally, diloxanide is formed by bacterial hydrolases. Diloxanide is for 90% absorbed and then metabolized to diloxanide glucuronide. The remaining 10% remains in the intestine as the active drug. Diloxanide is generally well tolerated. Adverse effects include flatulence, nausea and abdominal cramps. 

Diloxanide furoate is the furoate ester of 2,3-dichloro-4-hydroxy-A-methyl acetanilide. This antiamoebic drug was developed as a result of the discovery that various a,a-dichloroacetamides possessed an amoebicidal activity [1]. Diloxanide furoate is considered as a safe and effective drug for the treatment of asymptotic or mildly symptomatic persons who are passing cysts of Entameba histolytica [2,3], It acts principally in the bowel lumen, and is used in the treatment of the intestinal amoebiasis. It is less effective in amebic dysentery than in asymptotic infection, but the furoate gives high intestinal concentrations and is possibly more effective than metronidazole in the treatment of cyst passers [4],... 

The melting point of diloxanide furoate has been reported to be 114-116°C... 

The differential scanning calorimetry thermogram of diloxanide furoate is shown in Figure 2. The data were obtained using a DuPont TA-9900 thermal analyzer system interfaced with the DuPont data unit. The thermogram was recorded using a heating rate of 10°C/minute, over a temperature interval of 100-250°C. 

Figure 1. X-Ray powder diffraction pattern of diloxanide furoate.

Crystallographic Data from the X-Ray Powder Pattern of Diloxanide Furoate... 

Figure 2. Differential scanning calorimetry thermogram of diloxanide furoate.

Diloxanide furoate is very slightly soluble in water, soluble to the extent of 1 in 100 in alcohol, 1 in 25 of chloroform, and 1 in 130 of ether [7],... 

No partition coefficient data have been reported for diloxanide furoate, but a theoretical log P value of 1.42 0.55 has been obtaining using the predictive program of Advanced Chemistry Development Laboratories [50]. 

The ultraviolet absorption spectrum of diloxanide furoate was recorded on a Shimadzu model 1601 PC LJV/VIS spectrophotometer, and is shown in Figure 3. In aqueous solution, the spectrum exhibited a single absorption maximum located at 260 nm. For this band, the A o/ .ic , value was 700, and the molar absorptivity equal to 22970. 

The fluorescence spectrum of diloxanide furoate in aqueous methanol (concentration of 8 pg/mL) was recorded using a Perkin Elmer NPF-44B fluorimeter system. As shown in Figure 4, the excitation maximum was noted at 240 nm, which agrees well with the absorption maxima observed in the UVA IS studies. The emission maximum was found at 335 nm. 

The infrared absorption spectrum of diloxanide furoate is shown in Figure 5, and was obtained as a KBr disc using a Perkin Elmer infrared spectrophotometer. The principal peaks were observed at energies of... 

Figure 3. Ultraviolet absorption spectrum of diloxanide furoate.

The proton NMR speetrum of diloxanide furoate was obtained using a Bruker system operating at 300, 400 or 500 MHz. Standard Brucker software was used to execute recording of DEPT, COSY, and HETCOR spectra. The sample was dissolved in CH30H-d4, and all resonance bands were referenced to the tetramethylsilane internal standard. 

The mass spectrum of diloxanide furoate was obtained using a Shimadzu PQ-5000 mass spectrometer, with the parent ion undergoing collision with helium carrier gas. The mass spectrum is shown in Figure 9, and features a base peak at m/z = 95, a molecular ion peak at m/e = 328, as well as numerous other fragments. Table 4 summarizes the proposed mass fragmentation pattern. 

Clarke has reported that diloxanide furoate gives a blue color with the Folin-Ciocalteu Reagent, and also yields a yellow color when subjected to Libermann s test [7],... 

The British Pharmacopoeia describes a non-aqueous titration method for the determination of diloxanide furoate [6]. To perform the test, one dissolves 0.3 g of diloxanide furoate in 50 mL of anhydrous pyridine, and titrates to a potentiometric end point using 0.1 N tetrabutylammonium... 

Roy and Prakash have developed a conductimetric method for the determination of diloxanide furoate [13]. The drug undergoes hydrolysis on heating with aqueous sodium hydroxide, and the excess sodium hydroxide is then determined conductimetrically. The method is reported to be useful for the analysis of the raw material, as well as for the analysis of tablets. 

Srinath and Bagavant reported a spectrophotometric method for the analysis of binary mixtures of diloxanide furoate and tinidazole or metronidazole [14]. The mixtures were analyzed at 258 and 310 nm, and it was found that Beer s law was obeyed over the range of 10 to 25 jrg/mL of tinidazole and diloxanide furoate. Analyte recoveries were in the range of 98.2 to 101.9%. 

---