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

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Requena-Méndez, Ana, Davies, Geraint, Waterhouse, David, Ardrey, Alison, Jave, Oswaldo, López-Romero, Sonia Llanet, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Moore, David A J (2019) 'Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.'. The Journal of Antimicrobial Chemotherapy, Vol 74, Issue 2, pp. 416-424.

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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 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.

Item Type: Article
Subjects: QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 268 Antitubercular agents. Antitubercular antibiotics
QV Pharmacology > QV 38 Drug action.
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1093/jac/dky444
Depositing User: Stacy Murtagh
Date Deposited: 06 Dec 2018 16:06
Last Modified: 24 Jan 2019 10:46
URI: http://archive.lstmed.ac.uk/id/eprint/9749

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