Pharmacokinetics and serum concentrations of antimycobacterial drugs in adult Turkish patients

Int J Tuberc Lung Dis. 2013 Nov;17(11):1442-7. doi: 10.5588/ijtld.12.0771.

Abstract

Objective: To document the pharmacokinetics and serum concentrations of first-line anti-tuberculosis drugs in adult Turkish patients with pulmonary tuberculosis (PTB).

Design: Consenting 21 adult patients (aged 38 ± 4 years, 10 female and 11 male) with newly diagnosed active PTB participated in the study. Blood samples were collected 1, 2, 4, 6 and 24 h after simultaneous isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA) and ethambutol (EMB) ingestion. Serum concentration-time profiles, maximum serum concentrations, time to achieve maximum serum concentrations, the half-life and the areas under the serum concentration-time curve for each of the four drugs were determined.

Results: Wide variations in pharmacokinetic parameters were observed among patients. In respectively 8 (38%), 17 (81%), 3 (14%) and 1 (5%) patients, the maximum INH, RMP, PZA and EMB serum concentrations were below the accepted therapeutic concentrations.

Conclusion: Our data show that the serum concentrations of anti-tuberculosis drugs varied considerably in the study patients. Therapeutic drug monitoring is necessary to identify patients with subtherapeutic INH and RMP serum concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / blood*
  • Antitubercular Agents / pharmacokinetics*
  • Area Under Curve
  • Directly Observed Therapy
  • Drug Monitoring
  • Ethambutol / blood
  • Ethambutol / pharmacokinetics
  • Female
  • Half-Life
  • Humans
  • Isoniazid / blood
  • Isoniazid / pharmacokinetics
  • Male
  • Middle Aged
  • Pyrazinamide / blood
  • Pyrazinamide / pharmacokinetics
  • Rifampin / blood
  • Rifampin / pharmacokinetics
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / drug therapy*
  • Turkey
  • Young Adult

Substances

  • Antitubercular Agents
  • Pyrazinamide
  • Ethambutol
  • Isoniazid
  • Rifampin