title: Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis.
abstract: BACKGROUND
  Low concentrations of anti-tuberculosis drugs are related to drug resistance and treatment failure.
  
  
  OBJECTIVE
  To determine the prevalence of low plasma concentrations of anti-tuberculosis drugs.
  
  
  METHODS
  The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran. Drug samples were drawn 2 and 6 h post dose for isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA); related concentrations were determined using high-performance liquid chromatography. Plasma drug concentrations, duration of treatment, age, sex, liver enzyme levels, administered doses and smoking status were evaluated and recorded.
  
  
  RESULTS
  Among 60 patients recruited to the study, the mean (±SD) age was 54.2 (±20.9) years; 39 were female. The median peak plasma concentrations (C(max)) of INH, RMP and PZA were respectively 2.5, 4.0 and 43.6 μg/ml; 81% of the patients had drug plasma concentrations lower than the target ranges for at least one administered drug. Respectively 49.1%, 92.5% and 8.7% of the patients had low concentrations of INH, RMP and PZA.
  
  
  CONCLUSIONS
  The results indicate that RMP concentrations are below the reference range in most patients, while PZA is within the target range of the standard doses.
authors.affiliation: Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Masih Daneshvari Hospital, Tehran, Iran; Clinical Pharmacy Department, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: F
authors.initials: F
authors.lastname: Fahimi
authors.forename: P
authors.initials: P
authors.lastname: Tabarsi
authors.forename: F
authors.initials: F
authors.lastname: Kobarfard
authors.forename: B D
authors.initials: BD
authors.lastname: Bozorg
authors.forename: A
authors.initials: A
authors.lastname: Goodarzi
authors.forename: F
authors.initials: F
authors.lastname: Dastan
authors.forename: N
authors.initials: N
authors.lastname: Shahsavari
authors.forename: S
authors.initials: S
authors.lastname: Emami
authors.forename: M
authors.initials: M
authors.lastname: Habibi
authors.forename: J
authors.initials: J
authors.lastname: Salamzadeh
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007492:Iran; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012015:Reference Standards; D012016:Reference Values; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D062606:Tertiary Care Centers; D017211:Treatment Failure; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin