Abstract
Background:Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region.Aims:This study investigates CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 genetic polymorphisms influence on cloroquine/primaquine treatment.Patients & methods:Generalized estimating equations analyses were performed to determine the genetic influence in parasitemia and/or gametocytemia clearance over treatment time in 164 patients.Results:An effect of CYP2C8 low-activity alleles on treatment was observed (p = 0.01). From baseline to first day of treatment, wild-type individuals achieved greater reduction of gametocytes than low-activity allele carriers. CYP2C9 and CYP3A5 genes showed a trend for gametocytemia and parasitemia clearance rates.Conclusion:Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment.
Highlights
Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region
The WHO recommended as first choice treatment protocol for uncomplicated Plasmodium vivax malaria chloroquine (CQ) and primaquine (PQ) combined therapy, in CQ susceptible areas
CQ and PQ are metabolized by several CYP450 (CYP) isozymes
Summary
Chloroquine/primaquine is the current therapy to eliminate Plasmodium vivax infection in the Amazon region. Conclusion: Future studies should be performed to access the extent of CYP2C8, CYP2C9 and CYP3A5 gene polymorphisms influence on cloroquine/primaquine treatment. CQ is a 4-aminoquinoline derivative of quinine, and has been the most widely used antimalarial drug since 1946 This drug has effects as schizontocide and gametocide, and is metabolized by CYP450 isozymes 2C8, 3A4, 3A5 and, to a lesser extent, 2D6 [4,5,6]. PQ is metabolized by CYP1A2, CYP3A4, CYP2D6 and CYPC19 isoforms in different extent to form diverse metabolites [7,8,9,10] This drug could lead to severe hemolytic anemia in subjects with glucose-6-phosphate dehydrogenase (G6PD) deficiency and this condition needs to be investigated before PQ prescription in some populations [11]
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