CYP2D6 polymorphisms and the safety and gametocytocidal activity of single dose primaquine for P. falciparum

Genetic variation in CYP2D6, the gene producing the drug metabolizing enzyme cytochrome P450 2D6 (CYP2D6), influences plasma concentrations of PQ and its metabolites and is associated with PQ treatment failure in P. vivax. Using blood and saliva samples of varying quantity and quality from 8 clinical trials across Africa, (n=1076), we were able to genotype CYP2D6 for 774 samples (72%).

We determined whether genetic variation in CYP2D6 has implications for PQ efficacy in individuals with gametocytes at the time of PQ administration (n=554) and for safety in Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals treated with PQ (n=110). Individuals with genetically inferred CYP2D6 poor/intermediate metabolizer status had higher gametocyte prevalence on day 7 or 10 post PQ compared to those with extensive/ultrarapid CYP2D6 metabolizer status (OR = 1.79 [1.10, 2.90], p = 0.018).