Population mechanistic heamatotoxicity modeling of Dapsone in G6PD deficiency patients

Population mechanistic heamatotoxicity modeling of Dapsone in G6PD deficiency patients

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Several antimalarial drugs (e.g. dapsone, primaquine) have the propensity to destroy red blood cells in the human body. The damaging effects of these antimalarial drugs are strongly associated with genetic variants of the enzyme, glucose-6-phosphate dehydrogenase (G6PD), of the patients. Patients with normal activity of G6PD can tolerate these antimalarial drugs, whereas patients with lower G6PD activity experience different levels of red blood cell destruction. The underlying processes of this adverse reaction are still unclear. This study aims to systematically explain this adverse event using mathematical modelling on both a population and an individual level. This study will use dapsone as a model drug with the level of red blood cells after drug administration in each patient as an outcome. The individual G6PD status will be taken into consideration as a factor of the red blood cell destruction. This mechanistic model of the red cell destruction after drug administration can help us to understand this event, as well as predict its consequences. The red cell destruction model will be able to explain and predict the outcome of drug administration in this group of patients. Furthermore, such a model can determine the appropriate dose and dosing schedule in different patients with different G6PD status in order to minimize the adverse effect.

[{ "PostingID": 3128, "Title": "GSK-714703/005", "Description": "A multi-centre, randomised, double-blind, double dummy study comparing the efficacy and safety of chlorproguanil-dapsone-artesunate versus artemether-lumefantrine in the treatment of acute uncomplicated Plasmodium falciparum malaria in children and adolescents in Africa.

Medicine: artesunate/chlorproguanil/dapsone, Condition: Malaria, Falciparum, Phase: 3, Clinical Study ID: 714703/005, Sponsor: GSK" },{ "PostingID": 3129, "Title": "GSK-714703/006", "Description": "A multi-centre, randomised, double-blind study to compare the efficacy and safety of chlorproguanil-dapsone-artesunate versus chlorproguanil-dapsone in the treatment of acute uncomplicated Plasmodium falciparum malaria in children, adolescents and adults in Africa.

Medicine: artesunate/chlorproguanil/dapsone, Condition: Malaria, Falciparum, Phase: 3, Clinical Study ID: 714703/006, Sponsor: GSK" }]

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