Isoniazid, rifampicin and pyrazinamide plasma concentrations 2 and 6 h post dose in patients with pulmonary tuberculosis

Int J Tuberc Lung Dis. 2013 Dec;17(12):1602-6. doi: 10.5588/ijtld.13.0019.

Abstract

Background: Low concentrations of anti-tuberculosis drugs are related to drug resistance and treatment failure.

Objective: To determine the prevalence of low plasma concentrations of anti-tuberculosis drugs.

Methods: The study was performed among 60 pulmonary tuberculosis (TB) in-patients at a tertiary care university-affiliated hospital in Tehran, Iran. Drug samples were drawn 2 and 6 h post dose for isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA); related concentrations were determined using high-performance liquid chromatography. Plasma drug concentrations, duration of treatment, age, sex, liver enzyme levels, administered doses and smoking status were evaluated and recorded.

Results: Among 60 patients recruited to the study, the mean (±SD) age was 54.2 (±20.9) years; 39 were female. The median peak plasma concentrations (C(max)) of INH, RMP and PZA were respectively 2.5, 4.0 and 43.6 μg/ml; 81% of the patients had drug plasma concentrations lower than the target ranges for at least one administered drug. Respectively 49.1%, 92.5% and 8.7% of the patients had low concentrations of INH, RMP and PZA.

Conclusion: The results indicate that RMP concentrations are below the reference range in most patients, while PZA is within the target range of the standard doses.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antitubercular Agents / administration & dosage
  • Antitubercular Agents / blood
  • Antitubercular Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Drug Monitoring / methods
  • Drug Therapy, Combination
  • Female
  • Hospitals, University
  • Humans
  • Iran
  • Isoniazid / administration & dosage
  • Isoniazid / blood
  • Isoniazid / pharmacokinetics*
  • Male
  • Middle Aged
  • Pyrazinamide / administration & dosage
  • Pyrazinamide / blood
  • Pyrazinamide / pharmacokinetics*
  • Reference Standards
  • Reference Values
  • Rifampin / administration & dosage
  • Rifampin / blood
  • Rifampin / pharmacokinetics*
  • Tertiary Care Centers
  • Treatment Failure
  • Tuberculosis, Pulmonary / blood
  • Tuberculosis, Pulmonary / diagnosis
  • Tuberculosis, Pulmonary / drug therapy*

Substances

  • Antitubercular Agents
  • Pyrazinamide
  • Isoniazid
  • Rifampin