Impact of Plasmodium vivax malaria and antimalarial treatment on cytochrome P450 activity in Brazilian patients

• DOI: 10.1111/bcp.14574
• Publication Date: 2020-09-30T19:43:20Z
• Authors: Anne Cristine Alm...; Anna Beatriz Ribe...; Maria Paula Marques; Gisely Cardoso de...; Allyson Guimarães...; Erick Frota Gomes...; Larissa Wanderley...; Fernanda Rodrigue...; Wuelton Marcelo M...; Marcus Vinicius G...; Vera Lucia Lanchote; Guilherme Suarez‐...
• Keywords: Vivax malaria

To investigate the impact of Plasmodium vivax malaria and chloroquine-primaquine chemotherapy on CYP2D6 CYP2C19 activity in patients from Brazilian Amazon.Adult (n = 30) were given subtherapeutic doses phenotypic probes metoprolol (10 mg) omeprazole (2 three different stages illness: acute disease (study phase 1), post (phase 2) convalescence (stage 3). Plasma concentrations CYP-hydroxylated metabolites (α-OH 5-OH omeprazole) measured using LC/MS/MS. Two pharmacokinetic metrics used to estimate CYP activity: (a) ratio plasma probe/metabolite at 240 minutes after administration (b) areas under time-concentration curves for (AUC0-12h ). For statistical analysis, normalized respective values 3. Taqman assays genotyping. Cytokines levels cytometric bead array.Both omeprazole, cytokines IL-6, IL-8 IL-10 varied significantly across study phases (ANOVA P < 0.0001). Post hoc tests showed greater metoprolol:α-OH ratios 1 2 compared 3, larger omeprazole:5-OH than higher circulating 3.P. treatment altered metabolic phenotypes. inhibition is attributed a level proinflammatory cytokines, while suppression ascribed mainly chloroquine exposure.