title: Distribution of three antituberculous drugs and their metabolites in different parts of pathological vertebrae with spinal tuberculosis.
abstract: METHODS
  To detect drug concentration levels and metabolite using high-performance liquid chromatography.
  
  
  OBJECTIVE
  To map concentration levels of three antituberculous drugs and two metabolites in the abnormal osseous tissues around the foci of patients with spinal tuberculosis.
  
  
  BACKGROUND
  Concentration levels of antituberculous drugs in the focus of spinal tuberculosis has been reported. However, the mapping of drugs distribution in different regions surrounding the foci of tuberculosis vertebrae remains unexplored, as well as the metabolite of the drugs.
  
  
  METHODS
  Thirty-eight patients with spinal tuberculosis were assigned into sclerotic group (n = 13) and nonsclerotic group (n = 25) based on computed tomographic (CT) images. All patients received a chemotherapy 10 months with 2HRZE/8H(2)R(2)E(2). All patients received surgery after 4 weeks of chemotherapy. Samples of serum, ilium, and pathologic vertebral tissues, including the foci, sclerotic wall (if applicable), region I of abnormal osseous tissues (within 4 mm), and region II of abnormal osseous tissues (more than 4 mm) from the foci were collected during operation. Concentration levels and metabolite of three drugs were measured using high-performance liquid method for all samples. Differences of means within groups were evaluated by ANOVA and Dunnett post hoc. A significant levels was set at P < 0.05.
  
  
  RESULTS
  Concentration levels of drugs varied greatly in different regions of spinal tuberculosis vertebrae. Concentration levels of isoniazid and rifampin were higher than the effective bactericidal concentration (EBC) level and that of pyrazinamide was five times of the minimal inhibitory concentration in the region II of abnormal osseous tissues and the ilium of nonsclerotic group. Three drugs achieved EBC in the region I of abnormal osseous tissues in the nonsclerotic group but not in the sclerotic group. Except pyrazinamide no drugs and their metabolite were identified in the foci of the sclerotic group, whereas there is trace of drugs and their metabolite in the foci of the nonsclerotic group.
  
  
  CONCLUSIONS
  Three drugs resulted in an effective bactericidal concentration level in osseous tissues around the foci of spinal tuberculosis except the osseous tissues 4 mm surrounding the sclerotic wall. The results suggested that osseous tissues within 4 mm surrounding the sclerotic wall should be excised during the surgery.
authors.affiliation: Department of Orthopedic and Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Qingan
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jianming
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000379:methods / Q000592:standards; D011718:Pyrazinamide / Q000097:blood / Q000493:pharmacokinetics; D011859:Radiography; D012293:Rifampin / Q000097:blood / Q000493:pharmacokinetics; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D014399:Tuberculosis, Spinal / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin