Cytochrome P450-dependent toxic effects of primaquine on human erythrocytes

Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

“…PQ requires metabolic activation for its antiparasitic activity and toxic effects (22). Deamination of the primary amino group of the side chain by monoamine oxidase (MOA) and hydroxylation of the quinoline ring by CYP enzymes have been identified as the two major metabolic pathways of PQ in in vitro (22,23) and in vivo (24) systems. Even though the aldehyde, the deamination product of PQ by MOA, has not been detected, its oxidized product carboxyprimaquine has been identified as the major circulating metabolite of racemic PQ in humans (25) and animals (26,27).…”

Malaria por Plasmodium vivax y falla al tratamiento radical

“…Si bien el perfil metabólico de PQ no se ha dilucidado en su totalidad, sus metabolitos provocarían una lisis parasitaria por medio de radicales libres del oxígeno y disrupción en la cadena respiratoria 4 . Asimismo, estos productos metabólicos se asocian a los efectos adversos hematológicos como metahemoglobinemia 19 y anemia hemolítica en pacientes con déficit de la enzima glucosa-6P-deshidrogenasa 20 . Por otra parte, el metabolismo del hospedero podría interferir con la eficacia de la PQ.…”

Review: Improving the Therapeutic Index of 8-Aminoquinolines by the Use of Drug Combinations: Review of the Literature and Proposal for Future Investigations

“…Formation of methemoglobin by primaquine increased at least 10 times by coincubating red cells with human liver microsomes, and this metabolic conversion could also be accomplished by recombinant human CYPs 1A2, 3A4, 2D6, 2B6, and 2E1. 27 Inhibitors of CYPs 2B6, 2D6, and 3A4 caused significant inhibition of the methemoglobin formation mediated by the microsomes.…”