Disease relevance of Camoquine

• In the light of the global debate over the use of this drug, we conducted a systematic review of the effectiveness and tolerability of amodiaquine in the treatment of uncomplicated falciparum malaria [1].
• A retrospective analysis suggests that the frequency of severe neutropenia complicating amodiaquine taken prophylactically may be as high as 1 in 2000 [2].
• By contrast, the cure rate was significantly lower (p=0.022) with amodiaquine (51 [72%] of 71; there were 12 recrudescences in the amodiaquine group) [3].
• Amodiaquine-induced hepatitis. A report of seven cases [4].
• Although the antimalarial agents chloroquine, hydroxychloroquine, and amodiaquine are widely used to treat a variety of medical conditions, their behavioral toxicity and lethality are not generally recognized [5].

High impact information on Camoquine

• Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial [6].
• BACKGROUND: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries [6].
• Effectiveness of amodiaquine as treatment for chloroquine-resistant Plasmodium falciparum infections in Kenya [7].
• 4-Aminoquinoline resistance of Plasmodium falciparum: insights from the study of amodiaquine uptake [8].
• IC50 values for the HNMT inhibitor amodiaquine were 0.50, 0.48, and 0.40 microM, respectively, for enzyme from these same three sources [9].

Chemical compound and disease context of Camoquine

• The results suggest that amodiaquine is effective for the treatment of chloroquine-resistant falciparum malaria in Kenya [7].
• In eastern Thailand, 14 adults with moderately severe falciparum malaria were treated with intravenous amodiaquine dihydrochloride, loading dose 10 mg base/kg infused over 4 h followed by three further intravenous infusions of 5 mg base/kg at 24, 48, and 72 h [10].
• Many African countries currently use a sulfadoxine-pyrimethamine combination (SP) or amodiaquine (AQ) to treat uncomplicated Plasmodium falciparum malaria [11].
• Simple in vitro markers of direct toxicity and potential reactive metabolite formation suggest that these two compounds are no more toxic than amodiaquine and desethylamodiaquine [12].
• With regard to specific drugs, it is clear that because of its toxicity amodiaquine should no longer be used for chemoprophylaxis, and that pyrimethamine/sulfadoxine should, for the most part, be used only as a presumptive therapy [13].

Biological context of Camoquine

• Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical implications [14].
• The introduction and high prevalence of the SVMNT haplotype may reflect this and may raise concern regarding the use of amodiaquine in artemisinin-based combination therapies in Africa [15].
• Monodesethyl amodiaquine strongly depressed PMN chemotaxis and phagocytosis at concentrations as low as 10 micrograms/ml [16].
• There were extreme interindividual variations in sensitivity to the depressive effect of monodesethyl amodiaquine when the PMN oxidative burst was assayed in terms of luminol-amplified chemiluminescence or lucigenin-amplified chemiluminescence [16].
• Antibody responses to Plasmodium falciparum merozoite surface protein-1 and efficacy of amodiaquine in Gabonese children with P. falciparum malaria [17].

Anatomical context of Camoquine

• In the case of amodiaquine, the neutrophil response was restored by washing, except for stimulation with opsonized particles [18].
• From among them, a morpholino derivative cured mice infected by Plasmodium berghei and displayed a lower toxicity than amodiaquine upon mouse macrophages [19].
• Amodiaquin accumulation by mouse erythrocytes infected with Plasmodium berghei [20].
• The augmentation depended on the dose of amodiaquine, the optimum effect (40% increase in volume of gastric juice, 80% in acid output) being achieved with 2 mg/kg [21].
• It is well established that CQ and amodiaquine (AQ) accumulate in the parasite's food vacuole and inhibit heme polymerization, thereby increasing its efflux out of the food vacuole [22].

Associations of Camoquine with other chemical compounds

• 2. Consequently, the in vivo dealkylation of amodiaquine, to the less lipid-soluble desethylamodiaquine, is a likely contributor to therapeutic failure in vivo [12].
• Many well-known drugs listed in the modern pharmacopoeia have their origins in nature, including, for example, quinine from the bark of the Cinchona tree for the treatment of malaria, which has been followed by the subsequent development of the synthetic derivatives chloroquine, amodiaquine, primaquine and mefloquine [23].
• The PMN oxidative burst was markedly depressed by monodesethyl amodiaquine, whatever the assay technique (luminol-amplified chemiluminescence, lucigenin-amplified chemiluminescence, myeloperoxidase activity) or stimulus used (opsonized zymosan, phorbol myristate acetate, formylmethionyl leucyl phenylalanine) [16].
• 1 Amodiaquine was found to be a potent inhibitor in vitro of gastric histamine methyltransferase from human and canine corpus and from pig antrum [21].
• Two metabolites were identified: the C-5' glutathione adduct of amodiaquine, derived from both endogenous and exogenous glutathione, and 4-amino-7-chloroquinoline, which was presumed to be formed by hydrolysis of amodiaquine quinoneimine [24].

Gene context of Camoquine

• Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate [25].
• Treatment of rats with 10 mg/kg (single dose) amodiaquine resulted in 10% and 63% increases, respectively in the activities of liver superoxide dismutase and glutathione peroxidase (P<0.01), while the activity of liver catalase was significantly reduced by 26% compared to control [26].
• Following multiple dose (10 mg/kg for 4 consecutive days) amodiaquine treatment, activities of superoxide dismutase and glutathione peroxidase were increased by 30% and 133% respectively while catalase activity was decreased by 45% [26].
• The immunoglobulin G antibody response to different MSP-1 recombinant proteins was evaluated in plasma samples from Gabonese children with uncomplicated malaria who were treated with amodiaquine [17].
• Enzyme inhibition studies with ketoconazole-pretreated rats showed that both amodiaquine quinoneimine and desethylamodiaquine formation can be catalysed by cytochrome P450 [27].

Analytical, diagnostic and therapeutic context of Camoquine

• INTERPRETATION: The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal [6].
• A specific enzyme-linked immunosorbent assay (ELISA) was developed for the detection and characterisation of antibodies directed against amodiaquine (AQ), an anti-malarial drug associated with agranulocytosis and liver damage in man [28].
• One electron oxidation of the antimalarial drug amodiaquine by inorganic radicals was investigated by pulse radiolysis [29].
• The disposition of amodiaquine in man after oral administration [30].
• This metabolite has been isolated in milligram quantities from the urine of an amodiaquine-dosed individual by extraction and preparative high-performance liquid chromatography (HPLC) and standardized using nuclear magnetic resonance spectroscopy with internal standardization [31].

References