News Update on Amodiaquine Research: Dec – 2019

Amodiaquine induced agranulocytosis and liver damage.

Seven cases of blood disorder and 2 of liver injury that were in all probability thanks to amodiaquine treatment were studied. In 5 cases blood disorder was combined with liver injury, and in one case of primary liver injury moderate leukopenia was gift. 3 patients died. High total doses or prolonged period of treatment, or both, seem to favour the prevalence of those reactions. The agglomeration of 5 of the seven cases of blood disorder among six months in one medical centre indicates that the chance to learn quantitative relation of amodiaquine for protozoal infection prevention ought to be re-evaluated. [1]

Pharmacokinetics of Quinine, Chloroquine and Amodiaquine

Malaria is related to a discount within the general clearance and apparent volume of distribution of the chinchona alkaloids; this reduction is proportional to the sickness severity. there’s raised protein binding, preponderantly to α1-acid compound protein, and elimination half-lives (in healthy adults antimalarial drug t½z= eleven hours, Quinidex t½z=8 hours) ar prolonged by five hundredth. general clearance is preponderantly by viscus biotransformation to a lot of polar metabolites (quinine eightieth, Quinidex 65%) and also the remaining drug is eliminated unchanged by the excretory organ. antimalarial drug is well absorbed orally or following shot even in severe cases of protozoal infection (estimated bioavailability over 85%). antimalarial drug and antimalarial drug could cause probably fatal cardiovascular disease if given by shot. [2]

FREQUENCY OF SEVERE NEUTROPENIA ASSOCIATED WITH AMODIAQUINE PROPHYLAXIS AGAINST MALARIA

6 out of seven patients with severe leukopenia related to the utilization of amodiaquine for protozoal infection prevention amodiaquine (400 mg weekly) and proguanil (200 mg daily); one of those patients had additionally taken co-trimoxazole and another had taken sulphaguanidine. The seventh patient had taken amodiaquine alone, however at the next dose. A retrospective analysis suggests that the frequency of severe leukopenia complicating amodiaquine taken prophylactically could also be as high as one in 2000. [3]

From malaria to cancer: Computational drug repositioning of amodiaquine using PLIP interaction patterns

Drug locating identifies new indications for best-known medicine. Here we have a tendency to report locating of the protozoal infection drug amodiaquine as a possible anti-cancer agent. whereas most locating efforts emerge through good fortune, we’ve got devised a process approach, that exploits interaction patterns shared between compounds. As a test suit, we have a tendency to took the anti-viral drug brivudine (BVDU), that additionally has anti-cancer activity, and outlined 10 interaction patterns victimisation our tool PLIP. These patterns characterise BVDU’s interaction with its target s. victimisation PLIP we have a tendency to performed associate in silico screen of all structural knowledge presently obtainable and known the Food and Drug Administration approved protozoal infection drug amodiaquine as a promising locating candidate. [4]

Detection of Plasmodium falciparum K13 Propeller A569G Mutation after Artesunate-amodiaquine Treatment Failure in Niger

Background: Artemisinin (ART) resistance could be a drawback which will compromise the elimination of protozoal infection. it’s related to purpose mutations within the kelch cistron PF3D7_1343700 or K13 propellor (pfk13). A recent worldwide map of pfk13 polymorphisms disclosed over one hundred non-synonymous (NS) mutations. However, it remains unclear whether or not these mutations ar the results of drug pressure or the expression of a natural polymorphism, owing to the scarceness of in-vivo choice of pfK13 mutations knowledge in continent.

Methodology: This survey evaluates the association between mutations in PfK13 and therefore the response to treatment with artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ) at Gaya, Niger. Mutations in PfK13 before and when treatment were analyzed and used as proof for the choice of drug resistance following drug pressure. [5]

Reference

[1] Neftel, K.A., Woodtly, W., Schmid, M., Frick, P.G. and Fehr, J., 1986. Amodiaquine induced agranulocytosis and liver damage. Br Med J (Clin Res Ed), 292(6522), (Web Link)

[2] Krishna, S. and White, N.J., 1996. Pharmacokinetics of quinine, chloroquine and amodiaquine. Clinical pharmacokinetics, 30(4), (Web Link)

[3] Hatton, C.S.R., Bunch, C., Peto, T.E.A., Pasvol, G., Russell, S.J., Singer, C.R.J., Edwards, G. and Winstanley, P., 1986. Frequency of severe neutropenia associated with amodiaquine prophylaxis against malaria. The Lancet, 327(8478), (Web Link)

[4] From malaria to cancer: Computational drug repositioning of amodiaquine using PLIP interaction patterns
Sebastian Salentin, Melissa F. Adasme, Jörg C. Heinrich, V. Joachim Haupt, Simone Daminelli, Yixin Zhang & Michael Schroeder
Scientific Reports volume 7, (Web Link)

[5] Maman Laminou, I., Mahamane Lamine, M., Arzika, I., Mahamadou, B., Gora, D. and Dieye, A. (2018) “Detection of Plasmodium falciparum K13 Propeller A569G Mutation after Artesunate-amodiaquine Treatment Failure in Niger”, Journal of Advances in Biology & Biotechnology, 18(2), (Web Link)

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