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Effects of dosage, comorbidities, and food on isoniazid pharmacokinetics in Peruvian tuberculosis patients

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dc.contributor.author Requena-Méndez, Ana
dc.contributor.author Davies, Geraint
dc.contributor.author Waterhouse, David
dc.contributor.author Ardrey, Alison
dc.contributor.author Jave, Oswaldo
dc.contributor.author López-Romero, Sonia Llanet
dc.contributor.author Ward, Stephen A.
dc.contributor.author Moore, David Alexander James
dc.date.accessioned 2020-06-10T18:11:36Z
dc.date.available 2020-06-10T18:11:36Z
dc.date.issued 2014
dc.identifier.uri https://hdl.handle.net/20.500.12866/8019
dc.description.abstract Poor response to tuberculosis (TB) therapy might be attributable to subtherapeutic levels in drug-compliant patients. Pharmacokinetic (PK) parameters can be affected by several factors, such as comorbidities or the interaction of TB drugs with food. This study aimed to determine the PK of isoniazid (INH) in a Peruvian TB population under observed daily and twice-weekly (i.e., biweekly) therapy. Isoniazid levels were analyzed at 2 and 6 h after drug intake using liquid chromatography mass spectrometric methods. A total of 107 recruited patients had available PK data; of these 107 patients, 42.1% received biweekly isoniazid. The mean biweekly dose (12.8 mg/kg of body weight/day) was significantly lower than the nominal dose of 15 mg/kg/day (P < 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (Cmax) and area under the concentration-time curve from 0 to 6 h (AUC0-6) were 2.77 mg/liter and 9.71 mg . h/liter, respectively, for daily administration and 8.74 mg/liter and 37.8 mg . h/liter, respectively, for biweekly administration. There were no differences in the Cmax with respect to gender, diabetes mellitus (DM) status, or HIV status. Food was weakly associated with lower levels of isoniazid during the continuation phase. Overall, 34% of patients during the intensive phase and 33.3% during the continuation phase did not reach the Cmax reference value. However, low levels of INH were not associated with poorer clinical outcomes. In our population, INH exposure was affected by weight-adjusted dose and by food, but comorbidities did not indicate any effect on PK. We were unable to demonstrate a clear relationship between the Cmax and treatment outcome in this data set. Twice-weekly weight-adjusted dosing of INH appears to be quite robust with respect to important potentially influential patient factors under program conditions. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartofseries Antimicrobial Agents and Chemotherapy
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Food-Drug Interactions en_US
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject Anti-HIV Agents/therapeutic use en_US
dc.subject Antitubercular Agents/pharmacokinetics/therapeutic use en_US
dc.subject Area Under Curve en_US
dc.subject Comorbidity en_US
dc.subject Diabetes Mellitus/drug therapy/epidemiology/pathology en_US
dc.subject Dietary Fats/metabolism/pharmacokinetics en_US
dc.subject Drug Administration Schedule en_US
dc.subject Female en_US
dc.subject HIV Infections/drug therapy/epidemiology/pathology en_US
dc.subject Humans en_US
dc.subject Hypoglycemic Agents/therapeutic use en_US
dc.subject Isoniazid/pharmacokinetics/therapeutic use en_US
dc.subject Male en_US
dc.subject Middle Aged en_US
dc.subject Peru/epidemiology en_US
dc.subject Rifampin/pharmacokinetics/therapeutic use en_US
dc.subject Sex Factors en_US
dc.subject Treatment Outcome en_US
dc.subject Tuberculosis, Pulmonary/drug therapy/epidemiology/pathology en_US
dc.title Effects of dosage, comorbidities, and food on isoniazid pharmacokinetics in Peruvian tuberculosis patients en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/AAC.03258-14
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05
dc.relation.issn 1098-6596


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