Intra-individual effects of food upon the pharmacokinetics of rifampicin and isoniazid.
J Antimicrob Chemother
; 74(2): 416-424, 2019 02 01.
Article
em En
| MEDLINE
| ID: mdl-30412245
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Rifampina
/
Tuberculose Pulmonar
/
Interações Alimento-Droga
/
Ingestão de Alimentos
/
Isoniazida
/
Antituberculosos
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article