{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T14:16:28Z","timestamp":1788790588147,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,7,2]],"date-time":"2015-07-02T00:00:00Z","timestamp":1435795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Consleho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico"},{"name":"Funda\u00e7\u00e3o de Amparo a pesquisa do estado do Rio de Janeiro"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim of the present study was to investigate the impact of human visceral leishmaniasis (VL) and curative chemotherapy on the activity of cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 in patients from an endemic region in Brazil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult patients with parasitologically confirmed VL were given a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan, immediately before (Study phase 1), 2\u20133\u2009days (phase 2) and 3\u20136\u2009months (phase 3) after curative VL chemotherapy. CYP activity was assessed by the apparent clearance of midazolam (CYP3A), omeprazole\/5\u2010hydroxyomeprazol ratio in plasma (CYP2C19) and losartan\/E3174 ratio in urine (CYP2C9).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mean values (95% confidence interval) in phases 1, 2 and 3 were, respectively: log apparent midazolam clearance, 1.21 (1.10\u20131.31), 1.45 (1.32\u20131.57) and 1.35 (1.26\u20131.44)\u2009ml\u2009min<jats:sup>\u20131<\/jats:sup>\u2009kg<jats:sup>\u20131<\/jats:sup>; omeprazole\/5\u2010hydroxyomeprazole ratio, 0.78 (0.61\u20130.94), 0.45 (0.27\u20130.63) and 0.37 (0.20\u20100.55); losartan\/E3174 ratio, 0.66 (0.39\u20130.92), 0.35 (0.20\u20130.50) and 0.35 (0.16\u20130.53). Analysis of variance revealed significant differences in CYP3A (<jats:italic>P<\/jats:italic>= 0.018) and CYP2C19 (<jats:italic>P<\/jats:italic>= 0.008), but not CYP2C9 (<jats:italic>P<\/jats:italic>= 0.11) phenotypic activity, across the three study phases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during acute VL compared with post\u2010chemotherapy. We propose that increased plasma concentrations of proinflammatory cytokines during active disease account for the suppression of CYP activity. The failure to detect significant changes in CYP2C9 activity in the overall cohort may reflect differential effects of the inflammatory process on the expression of CYP isoforms, although the possibility of insufficient statistical power cannot be dismissed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12677","type":"journal-article","created":{"date-parts":[[2015,5,2]],"date-time":"2015-05-02T18:08:00Z","timestamp":1430590080000},"page":"1160-1168","source":"Crossref","is-referenced-by-count":22,"title":["Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients"],"prefix":"10.1111","volume":"80","author":[{"given":"Vera Lucia","family":"Lanchote","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Farmacocin\u00e9tica e Metabolismo, Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roque","family":"Almeida","sequence":"additional","affiliation":[{"name":"Universidade Federal de Sergipe Hospital Universit\u00e1rio Aracaju Sergipe Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldina","family":"Barral","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz (CPqGM) Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ) Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manoel","family":"Barral\u2010Netto","sequence":"additional","affiliation":[{"name":"Centro de Pesquisas Gon\u00e7alo Moniz (CPqGM) Funda\u00e7\u00e3o Oswaldo Cruz (FIOCRUZ) Salvador Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paula","family":"Marques","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacocin\u00e9tica e Metabolismo, Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e1lia V.","family":"Moraes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacocin\u00e9tica e Metabolismo, Departamento de An\u00e1lises Cl\u00ednicas, Toxicol\u00f3gicas e Bromatol\u00f3gicas Faculdade de Ci\u00eancias Farmac\u00eauticas de Ribeir\u00e3o Preto Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela M.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Universidade Federal de Sergipe Hospital Universit\u00e1rio Aracaju Sergipe Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania M. 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