Primaquine base

Primaquine base Soluble in ether, moderately soluble in water. 

Baird et al. [154] reported that primaquine base (30 mg/day) had protective efficacy against Plasmodium falciparum and P. vivax of 85-93%. Among 339... 

Primaquine base 0.5 mg/kg/day in the prophylaxis of Plasmodium falciparum and P. vivax malaria for a year did not cause noteworthy adverse effects. General... 

Primaquine phosphate USP. Tablets marketed in the U.S. contain 15 mg primaquine base per tablet (this may vary elsewhere) doses below are expressed as primaquine base. Primaquine may be used in special circumstances, such as when preferred agents cannot be tolerated or for multidrug-resistant P. falciparum. This should be done with caution and in consultation with malaria experts, such as those available through the CDC. The adult dose is 30 mg base (2 tablets) daily starting several days before exposure and continued for 7 days after exposure. The same regimen at a dose of 0.6 mg/kg base is used for children. Primaquine is contraindicated in G6PD deficiency or pregnancy see text). 

Bromo-5-phthalimido pentane is prepared by the interaction of 1, 4-dibromopentane with potassium phthalimide, which on reaction with 8-amino-6-methoxy quinoline yields the condensed product. Further treatment with hydrazine eliminates the phthalimido residue and yields the primaquine base which on reaction with a double molar quantity of phosphoric acid forms the official compoimd. 

It may also be prepared by the condensation of 2-ehloro-pentylamine with 8-amino-6-methoxy quinoline to obtain primaquine base which on treatment with bimolar quantity of phosphoric acid yields primaquine phosphate. 

When leaving an Primaquine (oral) 30 mg base (52.6 mg 0.6 mg/kg base (1 mg/kg Contraindicated in those with... 

The two-component lipid models were also characterized in the absence of sink conditions (Table 7.8). Comparisons between models 7.0 (Table 7.7) and 1.0 (Table 7.5) suggest that negative charge in the absence of sink causes the permeabilities of many of the bases to decrease. Exceptions are quinine, prazosin, primaquine, ranitidine, and especially metoprolol. The inclusion of 0.6% PA causes Pe of metoprolol to increase nearly 10-fold, to a value twice that of propranolol, a more lipophilic molecule than metoprolol (based on the octanol-water scale). Naproxen and ketoprofen become notably more permeable in the two-component system. Surprisingly, the neutral progesterone becomes significantly less permeable in this system. 

Primaquine diphosphate melts at about 197—198 °C and primaquine oxalate melts at 182.5—185 °C. Primaquine as a base is viscous liquid that boils at 175—179°C. Primaquine oxalate m.p. 182.5—185 °C. 

Walash et al. [10] determined primaquine and other quinoline drugs in bulk and in pharmaceuticals by a titrimetric method. The method is based on reaction with l,3-dibromo-5,5-dimethylhydantoin or TV-bromosuccinimide as the titrant. Primaquine was determined either by usual titration or by potentiometric titration with the brominating agents. The recovery was approximately 100%. The method was simple, precise, and accurate. 

Yang et al. [12] determined the ionization constants of primaquine by a titrimetric method and studied its coordination ratio with vitamin C. The ionization constants of primaquine in 50% (v/v) ethanol in water determined at 25 °C in the ionic strength range of 5 x 10 to 5 x 10-2 mol/L are given. The coordination ratio of primaquine to vitamin C is determined by continuous variation and mole ratio methods based on pH and conductance measurements to be 1 1, indicating that the coordination compound formed in the solution is mainly a 1 1 compound. 

Abou-Ouf et al. [16] described a spectrophotometric method for the determination of primaquine phosphate in pharmaceutical preparation. Two color reactions for the analysis of primaquine phosphate dosage form, which are based on 2,6-dichlor-oquinone chlorimide and l,2-naphthoquinone-4-sulfonate, were described. The reactions depend on the presence of active centers in the primaquine molecule. These are the hydrogen atoms at position 5 of the quinoline nucleus and the primary amino group of the side chain. The method was applied to tablets of primaquine phosphate and a combination of primaquine phosphate and amodiaquine hydrochloride. 

Abdel-Salam et al. [21] described a sensitive and simple spectrophotometric method for the determination of primaquine and other antimalarial drugs. The method is based on the formation of complexes between iodine (as an acceptor) and the basic drug in chloroform solution. Optimum conditions were established for the determination of primaquine, in pure form or in pharmaceutical preparation. Results were accurate and precise. 

Talwar et al. [26] described a difference spectrophotometric method for the estimation of primaquine phosphate in tablets. The method is based on the... 

Rao and Rao [33] used a rapid, sensitive, and simple colorimetric method for the estimation of primaquine phosphate. The method is based on its reaction with sodium vandate to give a pink color, which has an absorbance maximum at 550 nm. Beer s law is obeyed for 2-30 pg/mL. 

Issa et al. [34] used 2,3-dichloro-5,6-dicyano-p-benzoquinone for the spectropho-tometric determination of primaquine and other antimalarials. The drugs were determined in tablets by a spectrophotometric method based on the reaction with 2.3-d ich loro-5.6-dicyano-p-benzoquinone and measurement of the absorbance at 460 nm. The reaction occurred fastest in methanol and acetonitrile to yield a radical anion, which was detected by electron spin resonance. The color attained its maximum intensity after 5 min and remained stable for at least 1 h. The absorbance versus concentration curve obeyed Beer s law in the concentration range 1-4 mg per 100 mL. The recovery was 99.9-102.6%. 

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. 

El-Kommos and Emara [44] described a spectrophotometric method, for the determination of primaquine and other secondary aromatic amines pharmaceuticals, using 3-methylbenzothiazolin-2-one hydrazone. The method is based on oxidative coupling reaction of 3-methylbenzothiazolin-2-one hydrazone. 

Clark et al. [53] subjected primaquine to metabolic studies using microorganisms. A total of 77 microorganisms were evaluated for their ability to metabolize primaquine, of these, 23 were found to convert primaquine to one or more metabolites (thin-layer chromatography analysis). Preparative scale fermentation of primaquine with four different microorganisms resulted in the isolation of two metabolites, identified as 8-(3-carboxy-l-methylpropylamino)-6-methoxyquinoline and 8-(4-acetamido-l-methylbutylamino)-6-methoxyquinoline. The structures of the metabolites were proposed, based primarily on a comparison of the 13C NMR spectra of the acetamido metabolite and the methyl ester of the carboxy metabolite with that of primaquine. The structures of both metabolites were confirmed by direct comparison with authentic samples. 

Hufford and Baker [56] reported the assignments of the 13C NMR spectra of three derivatives of primaquine namely 4-methylprimaquine, 5-methoxy-4-methylprima-quine, and 5-methoxyprimaquine. These assignments were based on comparison with those of primaquine, proton-coupled data, and selective long-range proton decoupling. 

Dean et al. [93] used a high performance liquid chromatographic method for the simultaneous determination of primaquine and carboxyprimaquine in plasma with electrochemical detection. After the addition of the internal standard, plasma was deproteinized by the addition of acetonitrile. Nitrogen-dried supernatants, resuspended in mobile phase were analyzed on a C8 reversed-phase column. Limits of detection for primaquine and carboxyprimaquine were 2 and 5 ng/mL with quantitation limits of 5 and 20 ng/mL, respectively. The assay sensitivity and specificity are sufficient to permit quantitation of the drug in plasma for pharmacokinetics following low dose (30 mg, base) oral administration of primaquine, typically used in the treatment of malaria and P. carinii pneumonia. 

Fan et al. [106] developed a high performance capillary electrophoresis method for the analysis of primaquine and its trifluoroacetyl derivative. The method is based on the mode of capillary-zone electrophoresis in the Bio-Rad HPE-100 capillary electrophoresis system effects of some factors in the electrophoretic conditions on the separation of primaquine and trifluoroacetyl primaquine were studied. Methyl ephedrine was used as the internal standard and the detection was carried out at 210 nm. A linear relationship was obtained between the ratio of peak area of sample and internal standard and corresponding concentration of sample. The relative standard deviations of migration time and the ratio of peak area of within-day and between-day for replicate injections were <0.6% and 5.0%, respectively. 

Singhasivanon et al. [131] investigated the pharmacokinetics of primaquine in eight healthy subjects (four males and four females). The volunteers received 15 mg base of primaquine daily for 14 days. The results showed that the concentrationtime profiles in whole blood and in plasma were similar. The mean values ( SD) of the area under the curve of the last dose were significantly decreased when compared to the values of the first dose both in the whole blood and in plasma. 

In cases of primaquine sensitivity, erythrocytes were shown to be deficient in G-6-PDH activity and thus there is not sufficient NADPH2 for the reduction of GSSG by its reductase system. In such individuals lowered GSH levels in erythrocytes were found (B6, B8, Bll, S8, S24, and others). Furthermore, it can be shown that in these cases, when erythrocytes are incubated with acetylphenylhydrazine (B6, G18), the maintenance of even a lowered GSH level is not possible. The GSH stability test is based on this fact it measures virtually the G-6-PDH activity and not that of GSSGR. 

P vivax and P ovale infections Chloroquine (as above), then (if G6PD normal) primaquine, 52.6 (30 mg base)for 14 days ... 

Chloroquine is the drug of choice in the treatment of nonfalciparum and sensitive falciparum malaria. It rapidly terminates fever (in 24-48 hours) and clears parasitemia (in 48-72 hours) caused by sensitive parasites. It is still used to treat falciparum malaria in some areas with widespread resistance, in particular much of Africa, owing to its safety, low cost, antipyretic properties, and partial activity, but continued use of chloroquine for this purpose is discouraged, especially in nonimmune individuals. Chloroquine has been replaced by other drugs, principally artemisinin-based combination therapies, as the standard therapy to treat falciparum malaria in most endemic countries. Chloroquine does not eliminate dormant liver forms of P vivax and P ovale, and for that reason primaquine must be added for the radical cure of these species. 

Some strains of P vivax in New Guinea, Southeast Asia, Central and South America, and other areas are relatively resistant to primaquine. Liver forms of these strains may not be eradicated by a single standard treatment with primaquine and may require repeated therapy. Because of decreasing efficacy, the standard dosage of primaquine for radical cure of P vivax infection was recently doubled to 30 mg base daily for 14 days. 

Primaquine has been studied as a daily chemoprophylactic agent. Daily treatment with 30 mg (0.5 mg/kg) of base provided good levels of protection against falciparum and vivax malaria. However, potential toxicities of long-term use remain a concern, and primaquine is generally recommended for this purpose only when mefloquine, Malarone, and doxycycline cannot be used. 

A single dose of primaquine (45 mg base) can be used as a control measure to render P falciparum gametocytes noninfective to mosquitoes. This therapy is of no clinical benefit to the patient but will disrupt transmission. 

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