Short communication: High prevalence of the cytochrome P450 2C8*2 mutation in Northern Ghana

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Abstract
Summary: 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.

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