title: Impact of food intake on the pharmacokinetics of first-line antituberculosis drugs in Taiwanese tuberculosis patients.
abstract: OBJECTIVE
  Under the directly observed treatment, short course (DOTS) program, antituberculosis (anti-TB) medications were possibly taken at random time, regardless of whether it was prior to or after meals. This study was to evaluate the impact of food intake on pharmacokinetic profiles of first-line TB drugs in Taiwanese TB patients, as well as the relationship between drug levels and pharmacogenetics.
  
  
  METHODS
  This open-label, randomized, cross-over study included newly diagnosed Taiwanese TB patients treated between January 2010 and February 2011 at Taipei Medical University-Wan Fang Hospital. Rifater [a fixed-dose combination formulation of isoniazid (INH), rifampicin (RIF), and pyrazinamide (PZA)] and ethambutol (EMB) were given according to national TB guidelines. Blood samples were collected prior to and 1 hour, 2 hours, 4 hours, 6 hours, and 10 hours after dosing under fasting or postprandial conditions. Pharmacokinetic parameters of the maximum serum concentration (Cmax), time to Cmax, and area under the serum concentration-time curve from the beginning to the 10(th) hour (AUC0-10) were calculated.
  
  
  RESULTS
  Sixteen TB patients were included and received anti-TB treatment under the DOTS program after discharge. The overall effects showed that food intake reduced the mean Cmax (INH: 40.6%, RIF: 40.2%, EMB 34.4%, PZA: 24.4%) and AUC0-10 (INH: 21.3%, RIF: 26.4%, EMB: 12.2%, PZA: 12.0%). Meanwhile, food increased the time to Cmax (INH: 78.1%, RIF: 151.3%, EMB: 41.4%, PZA: 148.9%).
  
  
  CONCLUSIONS
  Significantly lower serum drug concentrations were observed under postprandial conditions than fasting conditions for INH, RIF, and PZA. The impact of taking random anti-TB drugs under the DOTS program instead of taking drugs regularly prior to meals requires further study.
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsien-Chun
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsing-Jin
authors.initials: HJ
authors.lastname: Liu
authors.affiliation: Division of Chest Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan. Electronic address: kjbai@wanfang.gov.tw.
authors.forename: Kuan-Jen
authors.initials: KJ
authors.lastname: Bai
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000493:pharmacokinetics*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D018592:Cross-Over Studies; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
keywords: first-line antituberculosis drugs; food; pharmacokinetics