{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:40:14Z","timestamp":1772628014526,"version":"3.50.1"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,11,12]],"date-time":"2014-11-12T00:00:00Z","timestamp":1415750400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            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 (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.001), and this effect was particularly marked in patients with concurrent diabetes and in males. The median maximum plasma concentration (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) and area under the concentration-time curve from 0 to 6 h (AUC\n            <jats:sub>0\u20136<\/jats:sub>\n            ) were 2.77 mg\/liter and 9.71 mg\u00b7h\/liter, respectively, for daily administration and 8.74 mg\/liter and 37.8 mg\u00b7h\/liter, respectively, for biweekly administration. There were no differences in the\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            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\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            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\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            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.\n          <\/jats:p>","DOI":"10.1128\/aac.03258-14","type":"journal-article","created":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T08:27:40Z","timestamp":1410856060000},"page":"7164-7170","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Effects of Dosage, Comorbidities, and Food on Isoniazid Pharmacokinetics in Peruvian Tuberculosis Patients"],"prefix":"10.1128","volume":"58","author":[{"given":"Ana","family":"Requena-M\u00e9ndez","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru"},{"name":"Barcelona Centre for International Health Research, CRESIB, Hospital Clinic-Universitat de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geraint","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Waterhouse","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Ardrey","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oswaldo","family":"Jave","sequence":"additional","affiliation":[{"name":"Servicio de Pneumolog\u00eda, Hospital Dos de Mayo, Lima, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia Llanet","family":"L\u00f3pez-Romero","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Molecular Parasitology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A. J.","family":"Moore","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru"},{"name":"TB Centre and Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60409-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis630"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-9-81"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.11.0503"},{"key":"e_1_3_2_6_2","volume-title":"Guidelines for treatment of tuberculosis","author":"WHO","year":"2010","unstructured":"WHO. 2010. Guidelines for treatment of tuberculosis. 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