Primaquine Failure and Cytochrome P-450 2D6 in Plasmodium vivax Malaria

Diagnosis and Treatment of Plasmodium vivax Malaria

“…A loss-of-function cytochrome-P450 2D6 genotype resulting in inadequate metabolism of PQ is an important cause of therapeutic failure, as occurred among two P. vivax experimental challenge subjects. 114 Safety considerations. The most common serious adverse effect (SAE) following PQ is intravascular hemolysis associated with the passage of dark or black urine and mild jaundice.…”

Malaria por Plasmodium vivax y falla al tratamiento radical

“…Bennet y cols. tipificaron el fenotipo del CYP 2D6 en 25 pacientes, asociando cinéticas de metabolismo intermedio y lento con falla al tratamiento radical 21 . La Organización Mundial de la Salud (OMS) recomienda un régimen de PQ 15 mg al día (0,25 mg/kg) durante 14 días para el tratamiento de las formas hepáticas de P. vivax, considerando ampliar a 30 mg al día (0,5 mg/ kg) en pacientes con malaria adquirida en zonas tropicales, particularmente en el Sudeste Asiático, Indonesia u Oceanía 3 .…”

A review of clinical pharmacokinetics of chloroquine and primaquine and their application in malaria treatment in Thai population

“…The total clearance is approximately 300 to 600 ml/min with renal clearance of less than 1% (3 to 20 ml/min) of the administered dose over 24 h. Hepatic metabolsim of PQ is via monoamine oxidases (A and B), cytochrome P450 (CYP3A4, CYP1A2, and CYP2D6), and flavin-containing monoamineoxygenase 3 enzymes. Several of the identified (for example, CPQ and 6-methoxy-8-aminoquinoline) and unidentified metabolites are detectable in plasma or urine (Constantino et al, 1999;Bennett et al, 2013;Pybus et al, 2013;Jin et al, 2014). The biotransformation pathways important for its therapeutic and toxic effects of PQ remain unclear, but recent evidence suggests that CYP2D6 may play a crucial role in generating the active intermediate metabolites (Constantino et al, 1999;Pybus et al, 2012;Bennett et al, 2013;Jin et al, 2014).…”

“…Several of the identified (for example, CPQ and 6-methoxy-8-aminoquinoline) and unidentified metabolites are detectable in plasma or urine (Constantino et al, 1999;Bennett et al, 2013;Pybus et al, 2013;Jin et al, 2014). The biotransformation pathways important for its therapeutic and toxic effects of PQ remain unclear, but recent evidence suggests that CYP2D6 may play a crucial role in generating the active intermediate metabolites (Constantino et al, 1999;Pybus et al, 2012;Bennett et al, 2013;Jin et al, 2014). The major plasma metabolite CPQ is however unlikely to be directly relevant to antimalarial activity .…”