Amodiaquine-Induced Agranulocytosis: Report of a Case with in vitro Studies of Granulocyte-Macrophage Progenitor Cells

Jp, Aymard; Rouveix, B; Ferry, Robert J.; Janot, C.; T, May; Legras, B; Streiff, F

doi:10.1159/000205276

Cited by 10 publications

(5 citation statements)

References 3 publications

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“…Amodiaquine (AQ) is a 4-aminoquinoline drug that has demonstrated sustainable efficacy compared to other anti-malarial drugs [ 7 - 9 ]. In view of low cost and high efficacy, AQ has been considered as a viable anti-malarial agent despite reported low risk of agranulocytosis during long term use [ 10 - 13 ]. Amodiaquine plus artesunate (AQ+AS), is recommended as an alternative first-line regimen to AL for the treatment of uncomplicated malaria in Uganda and many other African countries [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

Ntale

Obua

Mukonzo

et al. 2009

Malar J

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Background: Artemisinin combination therapy (ACT) has been widely adopted as first-line treatment for uncomplicated falciparum malaria. In Uganda, amodiaquine plus artesunate (AQ+AS), is the alternative first-line regimen to Coartem ® (artemether + lumefantrine) for the treatment of uncomplicated falciparum malaria. Currently, there are few field-adapted analytical techniques for monitoring amodiaquine utilization in patients. This study evaluates the field applicability of a new method to determine amodiaquine and its metabolite concentrations in whole blood dried on filter paper.

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Section: Introductionmentioning

confidence: 99%

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

Ntale

Obua

Mukonzo

et al. 2009

Malar J

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“…This is as reported in an in vitro study where AQ generated free radicals in the form of AQ quinone immine and semi quinone immine, and these have been implicated in lipid peroxidation in the membranes of hepatocyte cells (Maggs et al 1988). Though it has been shown in several cases that AQ-induced agranulocytosis occurs via Immune-mediated mechanisms, a direct toxic effect of the drug on abnormally sensitive myeloid progenitor cells has been reported (Aymard et al, 1989). This effect is based on the inhibition of the growth of blood colony forming cells (Rhodes et al, 1986).…”

Section: Introductionmentioning

confidence: 55%

The effect of amodiaquine on some brain macromolecules of Wistar rats

Ekong¹,

Igiri²,

Ekanem³

et al. 2009

International Journal of Biological and Chemical Sciences

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Amodiaquine (AQ) is a 4-aminoquinoline antimalarial with schizonticidal action against different strains of Plasmodia. This study assessed the effect of the drug on some macromolecules of the brain of albino Wistar rats. Twenty-four adult Wistar rats weighing between 150-180 g were divided into four groups of six animals each. Group 1 served as the control and received distilled water, while groups 2, 3 and 4, the experimental groups, were treated with 17.50 mg/kg, 8.75 mg/kg and 8.75 mg/kg of AQ, respectively. The treatment lasted three days for groups 2 and 3, and six days for group 4. The brains of the animals were removed, weighed and preserved in sucrose tris-KCl-MgCl (STKM) buffer for some macromolecule analysis. The total proteins (TP) and triacylglycerol (TAG) showed no significant (p>0.05) differences between the experimental groups compared to the control, and there was no significant (p>0.05) difference within the experimental groups. In the cholesterol (CH) estimation, the control had significantly (p<0.01, p<0.001) higher concentration than groups 3 and 4 respectively, but not group 2. CH concentration in group 2 was, however, significantly (p<0.05, p<0.01) higher than that in groups 3 and 4 respectively. These results reveal that AQ caused insignificant change to brain TP and TAG, but significantly altered the CH in the brain of Wistar rats.

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“…some case reports with in vilro bone marrow cultures (Lind et al, 1973;Rhodes et ul, 1986;Aymard et al 1989) are in support of a direct toxic effect on abnormally sensitive myeloid progenitor cells: accordingly, in virro GM-CFU cultures may prove useful in predicting amodiaquine myelotoxicity;…”

Section: Discussionmentioning

confidence: 96%

The in vitro effect of amodiaquine on bone marrow granulocyte‐macrophage progenitor cells from normal subjects

Aymard¹,

Wioland²,

Ferry³

et al. 1992

Fundamemntal Clinical Pharma

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Amodiaquine is used for antimalarial prophylaxis and treatment and has been associated with neutropenia and agranulocytosis in man. The effect of the drug on the in vitro growth of bone marrow human myeloid progenitor cells (GM-CFU) was tested using the soft agar culture technique: 42 haematologically normal subjects were studied and it was found that amodiaquine, at concentrations tested in vitro (0.005, 0.05 and 0.5 micrograms.ml-1), had no quantitative effect on the colony and cluster growth. Our results argue against direct toxicity of the drug on GM-CFU. Therefore, in cases of amodiaquine-associated neutropenia, alternative mechanisms should be considered: a abnormally sensitive GM-CFU; b) toxic effect of metabolites such as desethyl-amodiaquine; c) immune-mediated toxicity.

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Amodiaquine-Induced Agranulocytosis: Report of a Case with in vitro Studies of Granulocyte-Macrophage Progenitor Cells

Cited by 10 publications

References 3 publications

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

Field-adapted sampling of whole blood to determine the levels of amodiaquine and its metabolite in children with uncomplicated malaria treated with amodiaquine plus artesunate combination

The effect of amodiaquine on some brain macromolecules of Wistar rats

The in vitro effect of amodiaquine on bone marrow granulocyte‐macrophage progenitor cells from normal subjects

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