title: Pharmacokinetics of thrice-weekly rifampicin, isoniazid and pyrazinamide in adult tuberculosis patients in India.
abstract: To study the pharmacokinetics of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) in adult tuberculosis (TB) patients and examine factors that influence drug pharmacokinetics.
  
  
  
  Adult TB patients (n = 101) receiving thrice-weekly anti-tuberculosis treatment in the Revised National TB Control Programme (RNTCP) were studied. The study was conducted at steady state after directly observed drug administration. RMP, INH and PZA concentrations were estimated using high-performance liquid chromatography and NAT2 genotyping by real-time polymerase chain reaction.
  
  
  
  RMP peak concentration (Cmax) was sub-therapeutic (<8 μg/ml) in 88% of the patients. The Cmax of RMP, INH and PZA at 2 h was observed in respectively 83.2%, 97.0% and 92.1% of the patients. The Cmax and area under the curve from 0 to 8 h (AUC0-8) of PZA was lower in TB patients with diabetes mellitus than in non-diabetics. Significant associations were observed between the Cmax and the AUC0-8 of RMP, INH and PZA with drug doses; RMP with category of treatment; INH with smoking, body mass index and N-acetyl transferase 2 genotype; and PZA with sex and smoking.
  
  
  
  Several risk factors for drug concentration variations were identified. Two-hour post-dosing drug concentrations mimicked Cmax. A high proportion of TB patients had RMP Cmax below the expected range, which is a matter of concern.
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: A K
authors: AK
authors: Hemanth Kumar
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: T
authors: T
authors: Kannan
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: V
authors: V
authors: Chandrasekaran
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: V
authors: V
authors: Sudha
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: A
authors: A
authors: Vijayakumar
authors: National Institute for Research in Tuberculosis, Chennai.
authors: K
authors: K
authors: Ramesh
authors: Chennai Corporation, Chennai, India.
authors: J
authors: J
authors: Lavanya
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: S
authors: S
authors: Swaminathan
authors: National Institute for Research in Tuberculosis, Chennai, India.
authors: G
authors: G
authors: Ramachandran
mesh_terms: D000328:Adult; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D005260:Female; D060005:Genotyping Techniques; D006801:Humans; D007194:India; D007538:Isoniazid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011718:Pyrazinamide / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012293:Rifampin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018401:Sample Size; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D007538:Isoniazid; D012293:Rifampin