Free Content 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.

Keywords: CYP2C8 variants; Ghanaian children; adverse effects; amodiaquine

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1365-3156.2005.01525.x

Affiliations: 1: Institute of Tropical Medicine, Charité-University Medicine Berlin, Berlin, Germany 2: Institute for Clinical Research and Development (IKFE), Mainz, Germany 3: School of Medicine and Health Sciences, University for Development Studies, Tamale, Northern Region, Ghana

Publication date: December 1, 2005

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