title: Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.
abstract: OBJECTIVE
  The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM).
  
  
  METHODS
  Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC.
  
  
  RESULTS
  The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 μg/ml, respectively.
  
  
  CONCLUSIONS
  TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India.
authors.forename: A K Hemanth
authors.initials: AK
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India.
authors.forename: V
authors.initials: V
authors.lastname: Chandrasekaran
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India.
authors.forename: T
authors.initials: T
authors.lastname: Kannan
authors.affiliation: State TB Officer, Chennai, Tamil Nadu, India.
authors.forename: A Lakshmi
authors.initials: AL
authors.lastname: Murali
authors.affiliation: District TB Officer, Chennai, India.
authors.forename: J
authors.initials: J
authors.lastname: Lavanya
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India.
authors.forename: V
authors.initials: V
authors.lastname: Sudha
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India.
authors.forename: Soumya
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Department of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, India. geethar@nirt.res.in.
authors.forename: Geetha
authors.initials: G
authors.lastname: Ramachandran
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012293:Rifampin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014376:Tuberculosis / Q000097:blood* / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin
keywords: Anti-tuberculosis drug concentrations; Diabetes mellitus; Revised National Tuberculosis Control Programme; Tuberculosis