Universidad Peruana Cayetano Heredia

Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid

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dc.contributor.author Requena-Méndez, A.
dc.contributor.author Davies, G.
dc.contributor.author Waterhouse, D.
dc.contributor.author Ardrey, A.
dc.contributor.author Jave, O.
dc.contributor.author López-Romero, S.L.
dc.contributor.author Ward, S.A.
dc.contributor.author Moore, David Alexander James
dc.date.accessioned 2019-12-06T21:02:52Z
dc.date.available 2019-12-06T21:02:52Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/7461
dc.description.abstract Background: Poor response to TB therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic parameters can be affected by comorbidities or the interaction of drugs with food. Objectives This study aimed to determine the effect of food intake upon pharmacokinetics of rifampicin and isoniazid in a Peruvian population with TB. Methods: Rifampicin and isoniazid levels were analysed at 2, 4 and 6 h after drug intake in both fasting and non-fasting states using LC-MS methods. Results: Sixty patients participated in the study. The median rifampicin C max and AUC 0-6 were higher during fasting than non-fasting: 7.02 versus 6.59 mg/L (P = 0.054) and 28.64 versus 24.31 mg·h/L (P = 0.002). There was a statistically significant delay overall of non-fasting T max compared with the fasting state T max (P = 0.005). In the multivariate analysis, besides the effect of fasting, C max for females was 20% higher than for males (P = 0.03). Concerning isoniazid, there were significant differences in the C max during non-fasting (median = 3.51 mg/L) compared with fasting (4.54 mg/L). The isoniazid dose received had an effect upon the isoniazid levels (1.26, P = 0.038). In the multivariate analysis, isoniazid exposure during fasting was found to be 14% higher than during non-fasting (CI = 1.02-1.28, P < 0.001). Neither radiological extent of the disease nor consumption of food with drug intake nor pharmacokinetics of rifampicin or isoniazid was associated with a poorer treatment outcome. Conclusions: Rifampicin in particular and isoniazid pharmacokinetics were significantly affected by the intake of the drug with food between and within individuals. en_US
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartofseries Journal of Antimicrobial Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject adult en_US
dc.subject area under the curve en_US
dc.subject Article en_US
dc.subject drug exposure en_US
dc.subject ethambutol en_US
dc.subject fasting en_US
dc.subject female en_US
dc.subject food intake en_US
dc.subject human en_US
dc.subject isoniazid en_US
dc.subject liquid chromatography-mass spectrometry en_US
dc.subject lung tuberculosis en_US
dc.subject major clinical study en_US
dc.subject male en_US
dc.subject maximum concentration en_US
dc.subject observational study en_US
dc.subject Peruvian en_US
dc.subject pharmacokinetic parameters en_US
dc.subject pyrazinamide en_US
dc.subject rifampicin en_US
dc.subject short course therapy en_US
dc.subject time to maximum plasma concentration en_US
dc.subject treatment outcome en_US
dc.subject tuberculosis en_US
dc.title Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1093/jac/dky444
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.relation.issn 1460-2091


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