Genetic Variation in Cytochrome P450 Enzymes and Implications for Antimalarial Drug Metabolism in Anambra State

Cytochrome P450 (CYP) enzymes, particularly CYP2C8 and CYP3A4, play pivotal roles in the hepatic metabolism of antimalarial drugs including amodiaquine and lumefantrine. Genetic polymorphisms in CYP genes can produce poor metaboliser or ultra-rapid metaboliser phenotypes that influence drug efficacy and toxicity. This study characterised selected CYP2C8 and CYP3A4 polymorphisms in adult malaria patients attending secondary health facilities in Anambra State, South East Nigeria. A cross-sectional molecular study enrolled 150 participants with confirmed uncomplicated Plasmodium falciparum malaria. Genomic DNA was extracted from peripheral blood, and genotyping was performed for CYP2C8*2 (c.805A>T), CYP2C8*3, and CYP3A4*20 using allele-specific PCR and Sanger sequencing. Allele frequencies were estimated and compared with published African reference populations. CYP2C8*2, previously reported at elevated frequencies in African populations, was detected at a clinically relevant frequency in this Anambra cohort. These findings have direct implications for personalised antimalarial pharmacotherapy and reinforce the need for pharmacogenomics integration into malaria treatment protocols in South East Nigeria. Keywords: CYP2C8, pharmacogenomics, antimalarial, Anambra State, drug metabolism