RESUMEN

Recently, Ghana has changed the first-line treatment of uncomplicated malaria from chloroquine to amodiaquine (AQ) plus artesunate. AQ may cause adverse events such as agranulocytosis and hepatoxicity. The pro-drug AQ is transformed by cytochrome P450 CYP2C8 to the active metabolite N-desethylaminodiaquine. Several polymorphic variants of CYP2C8 are known, some with reduced activity. In 200 randomly selected children from Northern Ghana, we determined the allele frequencies of the CYP2C8 variants CYP2C8*1 (wild type), CYP2C8*2, CYP2C8*3, and CYP2C8*4. We did not detect CYP2C8*3 and CYP2C8*4, but CYP2C8*2 showed an allele frequency of 0.1675. AQ metabolism in patients with CYP2C8*2 may be impaired, and with an increase of AQ based treatment the risk of severe adverse events may mount.

Asunto(s)

Hidrocarburo de Aril Hidroxilasas/genética , Malaria Falciparum/genética , Mutación , Amodiaquina/efectos adversos , Amodiaquina/uso terapéutico , Antimaláricos/efectos adversos , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Artesunato , Niño , Preescolar , Citocromo P-450 CYP2C8 , Quimioterapia Combinada , Femenino , Frecuencia de los Genes , Ghana , Humanos , Lactante , Malaria Falciparum/tratamiento farmacológico , Masculino , Polimorfismo Genético/genética , Prevalencia , Profármacos/efectos adversos , Profármacos/uso terapéutico , Sesquiterpenos/uso terapéutico