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Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid
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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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REQUENA-MÉNDEZ, Ana, DAVIES, Geraint, WATERHOUSE, David, ARDREY, Alison, JAVE, Oswaldo, LLANET LÓPEZ-ROMERO, Sonia, WARD, Stephen a., MOORE, David a. j.. Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid. _Journal of Antimicrobial Chemotherapy_. 2019. Vol. 74, núm. 2, pàgs. 416–424. [consulta: 30 de gener de 2026]. ISSN: 0305-7453. [Disponible a: https://hdl.handle.net/2445/128328]