title: Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome.
abstract: Therapeutic drug monitoring in tuberculosis remains controversial. We evaluated the relationship between antituberculosis drug levels in blood and clinical outcome. Serum concentrations of first-line antituberculosis drugs were measured in tuberculosis patients between March 2006 and April 2013. Venous blood was drawn 2 h after drug ingestion and was analyzed using high-performance liquid chromatography-tandem mass spectrometry. We retrospectively reviewed the data and determined the association of serum drug levels with clinical outcome. Among 413 patients, the prevalences of low serum concentrations of isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA) were 59.9%, 27.8%, 12.8%, and 8.7%, respectively. The low INH group had a greater percentage of patients with a history of tuberculosis treatment (19.2% versus 11.0%; P = 0.026) and was more likely to present with drug-resistant strains (17.6% versus 8.8%; P = 0.049) than the normal INH group; however, low levels of INH, RMP, EMB, and PZA were not related to treatment outcome. Low INH level had a tendency to be associated with 2-month culture positivity, but it was not statistically significant (P = 0.072) in multivariate analysis. Seventeen (4.1%) patients experienced a recurrence. However, the recurrence rate was not statistically different between the low and normal INH groups. Low serum INH may play a role in recurrence and in acquired drug resistance. However, the serum level of INH was not directly related to either treatment response or recurrence rate. The role and usefulness of therapeutic drug monitoring should be evaluated in further prospective studies.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Jong Sun
authors.initials: JS
authors.lastname: Park
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Jae-Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Yeon Joo
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Se Joong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Young-Jae
authors.initials: YJ
authors.lastname: Cho
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Ho Il
authors.initials: HI
authors.lastname: Yoon
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea.
authors.forename: Junghan
authors.initials: J
authors.lastname: Song
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, South Korea jhlee7@snubh.org.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D002853:Chromatography, Liquid; D016903:Drug Monitoring; D004977:Ethambutol / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development; D011718:Pyrazinamide / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D012008:Recurrence; D012189:Retrospective Studies; D012293:Rifampin / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D004977:Ethambutol; D007538:Isoniazid; D012293:Rifampin