Effect of peritoneal dialysis on plasma and peritoneal fluid concentrations of isoniazid, pyrazinamide, and rifampin

Perit Dial Int. 2003 Jul-Aug;23(4):362-7.

Abstract

Objective: This study was performed to elucidate the pharmacokinetic profiles of antimycobacterial regimens for peritoneal dialysis patients.

Patients: Nine patients on maintenance continuous ambulatory peritoneal dialysis (CAPD) were included in this study.

Methods: After administering a conventional oral dose of antituberculosis medications, we measured plasma and peritoneal fluid concentrations of isoniazid by fluorometry, and rifampin and pyrazinamide by high performance liquid chromatography. The assay data were subjected to pharmacokinetic analysis.

Results: Average peak plasma concentrations of isoniazid, rifampin, and pyrazinamide were 3.3 mg/L, 6.5 mg/L, and 30.9 mg/L, respectively, all of which much exceed the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. Peritoneal fluid concentrations of isoniazid and pyrazinamide were maintained well above the MICs for M. tuberculosis; however, peritoneal fluid concentration of rifampin was below the therapeutic range most of the time.

Conclusion: For the treatment of systemic or pulmonary tuberculosis in CAPD patients, no dose adjustments are required for isoniazid, rifampin, or pyrazinamide. On the contrary, for the treatment of tuberculous peritonitis, oral rifampin therapy is not expected to be effective because of its low peritoneal fluid concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antitubercular Agents / analysis
  • Antitubercular Agents / blood
  • Antitubercular Agents / pharmacokinetics*
  • Ascitic Fluid / chemistry*
  • Female
  • Humans
  • Isoniazid / analysis
  • Isoniazid / blood
  • Isoniazid / pharmacokinetics*
  • Male
  • Middle Aged
  • Peritoneal Dialysis, Continuous Ambulatory / methods*
  • Pyrazinamide / analysis
  • Pyrazinamide / blood
  • Pyrazinamide / pharmacokinetics*
  • Rifampin / analysis
  • Rifampin / blood
  • Rifampin / pharmacokinetics*

Substances

  • Antitubercular Agents
  • Pyrazinamide
  • Isoniazid
  • Rifampin