Requena-Mendez, Ana, Davies, Geraint 
ORCID: 0000-0002-3819-490X, Waterhouse, David, Ardrey, Alison, Jave, Oswaldo, Llanet Lopez-Romero, Sonia, Ward, Stephen A and Moore, David AJ
(2019)
Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 74 (2).
pp. 416-424.
Abstract
<h4>Background</h4>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.<h4>Objectives</h4>This study aimed to determine the effect of food intake upon pharmacokinetics of rifampicin and isoniazid in a Peruvian population with TB.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>Rifampicin in particular and isoniazid pharmacokinetics were significantly affected by the intake of the drug with food between and within individuals.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Tuberculosis, Pulmonary, Isoniazid, Rifampin, Antitubercular Agents, Treatment Outcome, Fasting, Multivariate Analysis, Eating, Food-Drug Interactions, Adult, Middle Aged, Female, Male, Young Adult, Biological Variation, Individual |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 28 May 2021 08:59 |
| Last Modified: | 18 Jan 2023 23:32 |
| DOI: | 10.1093/jac/dky444 |
| Open Access URL: | https://archive.lstmed.ac.uk/9749/ |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3101740 |
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