Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.
Requena-Méndez, Ana;
Davies, Geraint;
Waterhouse, David;
Ardrey, Alison;
Jave, Oswaldo;
López-Romero, Sonia Llanet;
Ward, Stephen A;
Moore, David AJ;
(2018)
Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.
The Journal of antimicrobial chemotherapy, 74 (2).
pp. 416-424.
ISSN 0305-7453
DOI: https://doi.org/10.1093/jac/dky444
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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.