Chloroquine base

A 16-year old girl was treated empirically with chloroquine (total 450 mg of chloroquine base) for fever, had no malarial parasites in the peripheral blood smear, but had severe hypoglycemia of 1.5 mmol/1 (27 mg/dl) (49). 

Clarke (8) reported that the principal peaks for chloroquine base in KBr disc are 1573, 1538, 1372 or 1448. 

The H-NMR spectra of chloroquine base and phosphate are shown in Fig. 5 and 6 and were obtained on Varian T6-A NMR Spectrometer with CDCI3 and D 0 respectively as solvents and tetramethylsilane as an internal reference. The signals are assigned in Table 2. 

The total dose of chloroquine base over 3 days should be approximately 25 mg/kg base. This is sufficient for Plasmodium malariae infection but, for Plasmodium vivax and Plasmodium ovale eradication of the hepatic parasites is necessary to prevent relapse, by giving ... 

The active component of many drugs, whether acid or base, is relatively insoluble and may present a problem in formulation. This is overcome by adding an acid to a base or vice versa the weight of the salt differs according to the acid or base component, i.e. chloroquine base 150 mg = chloroquine sulphate 200 mg = chloroquine phosphate 250 mg (approximately). Where there may be variation, therefore, the amount of drug prescribed is expressed as the weight of the active component, in the case of chloroquine, the base. 

A dapsone syndrome was reported in a 30-year-old woman after 4 weeks of treatment with Maloprim and chloroquine base 300 mg/weekly. The symptoms comprised fever, joint and muscle pains, dry cough, and a diffuse red urticarial rash, followed by generalized lym-phadenopathy, a painful exudative tonsillitis, and a prominent atypical lymphocytosis. 

P. and good tolerance.The daily administration of 25 mg of DDS concurrently with 300 mg of chloroquine base and mg of primaquine weekly proved highly effective in preventing patency following challenges with two strains of chloroquine-resistant P. falciparum... 

Condensation of the nucleus and the side ehain gives rise to the chloroquine base which on treatment with hot phosphoric acid in an ethanolic solution yields the official compoimd. 

Six healthy subjects were given chloroquine phosphate 1 g (equivalent to 620 mg of chloroquine base) with either magnesium trisiUcate 1 g or... 

Cimetidine 400 mg daily for 4 days approximately halved the clearance of a single 600-mg dose of chloroquine base in 10 healthy subjects. The elimination half-life was prolonged from 3.11 to 4.62 days. It was suggested that these effects occurred because cimetidine inhibits the metabolism of chloroquine by the liver. The clinical importance of this interaction is uncertain, but it would seem prudent to be alert for any signs... 

Following the observation that mouth ulcers appeared to be common in those taking prophylactic antimalarials, an extensive study was undertaken in 628 servicemen in Belize. Of those taking proguanil 200 mg daily, 24% developed mouth ulcers, and in those also taking chloroquine base 150 to 300 mg weekly, 37% developed mouth ulcers. The incidence of diarrhoea was also increased from 63% among those who did not develop ulcers to 83% in those that did develop ulcers (any treatment). The reasons are not understood. The authors of the study suggested that these two... 

A study in which healthy subjects were given azithromycin 1 g daily for 3 days either alone or with chloroquine base 600 mg daily on days 1 and 2, and 300 mg on day 3, found no pharmacokinetic interaction. ... 

Amodiaquine, a Mannich base 4-aminoquinoline, eliminates blood stage parasites. Its mode of action is similar to that of chloroquine (see below) and there is some cross-resistance. 

Navarro, M., Vasquez, F., Sanchez-Delgado, R.A., Perez, H., Sinou, V. and Schrevel, J. (2004) Toward a Novel Metal-Based Chemotherapy against Tropical Diseases. 7. Synthesis and in Vitro Antimalarial Activity of New Gold-Chloroquine Complexes. Journal of Medicinal Chemistry, 47, 5204. 

In an uncomplicated attack of malaria (for all plasmodia except chloroquine-resistant P. falciparum and P. vivax), the recommended regimen is chloroquine 600 mg (base) initially, followed by 300 mg (base) 6 hours later, and then 300 mg (base) daily for 2 days.3 In severe illness or falciparum malaria, patients should be admitted to an acute care unit and quinidine gluconate 10 mgsalt/kg... 

Chloroquine- Chloroquine 300 mg (base) once 5 mg (base)/kg of body Hydroxychloroquine sulfate 310... 

El-Ashry et al. [36] studied the complex formation between the bromophenol blue, primaquine, and other important aminoquinoline antimalarials. The colorimetric method used was described as simple and rapid and is based on the interaction of the drug base with bromophenol blue to give a stable ion-pair complex. The spectra of the complex show maxima at 415 420 nm with high apparent molar absorptivities. Beer s law was obeyed in the concentration range 1-8,2-10, and 2-12 pg/mL for amodiaquine hydrochloride, primaquine phosphate, and chloroquine phosphate, respectively. The method was applied to the determination of these drugs in certain formulations and the results were favorably comparable to the official methods. 

The answer is c. (Hardman, pp 970-972.) Chloroquine is a 4-aminoquinoline derivative that selectively concentrates in parasitized red blood cells. It is a weak base, and its alkalinizing effect on the acid vesicle of the parasite effectively destroys the viability of the parasite. 

Chagas disease is caused by a kinetoplastid trypanosoma parasite and affects millions of people in Latin America. The disease is currently incurable. Chemotherapy is based mainly on nitrofuran and nitroimidazole compounds and sterol biosynthesis inhibitors such as ketoconazole (337). Toxicity and high doses are the major problems for these organic drugs. Urbina et al. (338, 339) have found that com-plexation of antiparasitic organic agents such as chloroquine (78)... 

Increased bilirubin levels are caused due to the intake of large doses of such drugs as chloroquine, vitamin K, sulpha-drugs, tetracyclines, paracetamol, nicotinic acid and monoamine oxidase inhibitors (e.g., iproniazid RP 1.0 nialamide RP 1.8 isocarboxazid RP 3.1 phenelzine RP 18 pheniprazine RP31 and tranylcypromine RP 45), where RP designates the Relative Potency based on the tiyptamine potentiation test. The elevated levels are due to hepatic injury, and... 

Here r and r refer to the predominant chloroquine, K E is the product of the intrinsic equilibrium constant for ethidium binding and an experimental efficiency factor,(53) Cbp is the total concentration of base pairs, and... 

Figure 4.15. Effect of chloroquine on linear pBR322 DNA. Torsion constant (top) and fluorescence amplitude ratio of the slow (intercalated) and fast (free) components in the decay of the ethidium fluorescence intensity (hottom) versus ln(added chl/bp). The DNA is present in 0.1 M NaCl, 10 mM Tris, 10 mM EDTA, pH 8.5, at 20°C, and ethidium is present at 1 dye per 300 base pairs. The points at the left of the figure apply for zero added chloroquine. The best-fit...

The weak base chloroquine (30-300 pM, 30 minutes, either in the presence or absence of serum) increases the endosomal pH (83) within a few minutes (45), leading to pH values close to 6.3 in both endosomes and lysosomes and therefore preventing lysosomal degradation. As a mechanism of action, a direct inhibition of lysosomal hydrolases (cathepsin B1 and some phospholipases and lysophospholipases) is reported (82). In Kupffer cells, effects are tolerated at concentrations of 40 pM or less for up to four hours and are irreversible within two hours after medium replacement (82). 

---