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Título:
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Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid
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Autores:
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Requena-Mendez, Ana ;
Davies, Geraint ;
Waterhouse, David ;
Ardrey, Alison ;
Jave, Oswaldo ;
Lopez-Romero, Sonia Llanet ;
Ward, Stephen A. ;
Moore, David A. J.
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Tipo de documento:
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texto impreso
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Editorial:
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Oxford University Press, 2018-11-30T17:17:14Z
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Nota general:
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info:eu-repo/semantics/restrictedAccess
https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
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Idiomas:
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Inglés
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Palabras clave:
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Editados por otras instituciones
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Artículos
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Artículos en revistas indizadas
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Resumen:
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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 Cmax and AUC0-6 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 Tmax compared with the fasting state Tmax (P?=?0.005). In the multivariate analysis, besides the effect of fasting, Cmax for females was 20% higher than for males (P?=?0.03). Concerning isoniazid, there were significant differences in the Cmax 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.
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En línea:
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https://academic.oup.com/jac/advance-article-abstract/doi/10.1093/jac/dky444/5166733?redirectedFrom=fulltext
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