User:Juliephg/sandbox

Pharmacogenetics
Amodiaquine has become an important drug in the combination therapy for malaria treatment in Africa. Amodiquine is bioactivated hepatically to its primary metabolite N-desethylamodiaquine by the cytochrome p450 enzyme CYP2C8. Among amodiaquine users, several rare but serious side effects have been reported and linked to variants in the CYP2C8 alleles. CYP2C8*1 is characterized as the wild-type allele, which shows an acceptable safety profile while CYP2C8*2, *3 and *4 all show a range of “poor metabolizer” phenotypes. People that are poor metabolizers of amodiaquine display lower efficacy against malaria as well as increased toxicity. Several studies have been conducted to determine the prevalence of CYP2C8 alleles amongst malaria patients in Eastern Africa, and have tentatively shown that the variant alleles have significant prevalence in that population. About 3.6% of the population studied shows high risk for a poor reaction to or reduced treatment outcomes when treated with amodiaquine. This information is useful in developing programs of pharmacovigilance in East Africa. These findings have important clinical considerations for prescribing anti-malarial medications in regions with high CYP2C8 variant frequency.