Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients

dc.creatorLanchote, Vera Lucia
dc.creatorAlmeida, Roque Pacheco de
dc.creatorBarral, Aldina Maria Prado
dc.creatorBarral Netto, Manoel
dc.creatorMarques, Maria Paula
dc.creatorMoraes, Natália Valadares de
dc.creatorSilva, Angela Maraia da
dc.creatorSouza, Tania M. V
dc.creatorKurtz, Guilherme Suarez
dc.date2016-04-12T13:12:51Z
dc.date2016-04-12T13:12:51Z
dc.date2015
dc.date.accessioned2023-09-26T23:51:26Z
dc.date.available2023-09-26T23:51:26Z
dc.identifierLANCHOTE, V. L. et al. Impact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients. British Journal of Clinical Pharmacology, v. 80, n. 5, p. 1160-1168, 2015.
dc.identifier1365-2125
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/13709
dc.identifier10.1111/bcp.12677
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8894951
dc.descriptionAIMS: 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. METHODS: Adult patients with parasitologically confirmed VL were given a CYP phenotyping cocktail, comprising midazolam, omeprazole and losartan, immediately before (Study phase 1), 2-3 days (phase 2) and 3-6 months (phase 3) after curative VL chemotherapy. CYP activity was assessed by the apparent clearance of midazolam (CYP3A), omeprazole/5-hydroxyomeprazol ratio in plasma (CYP2C19) and losartan/E3174 ratio in urine (CYP2C9). RESULTS: Mean values (95% confidence interval) in phases 1, 2 and 3 were, respectively: log apparent midazolam clearance, 1.21 (1.10-1.31), 1.45 (1.32-1.57) and 1.35 (1.26-1.44) ml min(-1) kg(-1) ; omeprazole/5-hydroxyomeprazole ratio, 0.78 (0.61-0.94), 0.45 (0.27-0.63) and 0.37 (0.20-0.55); losartan/E3174 ratio, 0.66 (0.39-0.92), 0.35 (0.20-0.50) and 0.35 (0.16-0.53). Analysis of variance revealed significant differences in CYP3A (P = 0.018) and CYP2C19 (P = 0.008), but not CYP2C9 (P = 0.11) phenotypic activity, across the three study phases. CONCLUSION: The phenotypic activities of CYP3A4 and CYP2C19 were significantly reduced during acute VL compared with post-chemotherapy. 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherBritish Pharmacological Society
dc.rightsopen access
dc.subjectLeishmaniose
dc.subjectLeishmaniose visceral
dc.subjectQuimioterapia
dc.subjectInflamação
dc.subjectAdultos
dc.subjectCitocromo-P450
dc.titleImpact of visceral leishmaniasis and curative chemotherapy on cytochrome P450 activity in Brazilian patients
dc.typeArticle


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