Clinical Pharmacokinetics

, Volume 40, Issue 5, pp 327–341

Comparative Pharmacokinetics and Pharmacodynamics of the Rifamycin Antibacterials

  • William J. Burman
  • Keith Gallicano
  • Charles Peloquin
Review Article Drug Disposition

DOI: 10.2165/00003088-200140050-00002

Cite this article as:
Burman, W.J., Gallicano, K. & Peloquin, C. Clin Pharmacokinet (2001) 40: 327. doi:10.2165/00003088-200140050-00002

Abstract

The rifamycin antibacterials, rifampicin (rifampin), rifabutin and rifapentine, are uniquely potent in the treatment of patients with tuberculosis and chronic staphylococcal infections.

Absorption is variably affected by food; the maximal concentration of rifampicin is decreased by food, whereas rifapentine absorption is increased in the presence of food. The rifamycins are well-known inducers of enzyme systems involved in the metabolism of many drugs, most notably those metabolised by cytochrome P45O (CYP) 3A. The relative potency of the rifamycins as CYP3A inducers is rifampin > rifapentine > rifabutin; rifabutin is also a CYP3A substrate.

The antituberculosis activity of rifampicin is decreased by a modest dose reduction from 600 to 450mg. This somewhat surprising finding may be due to the binding of rifampicin to serum proteins, limiting free, active concentrations of the drug. However, increasing the administration interval (after the first 2 to 8 weeks of therapy) has little effect on the sterilising activity of rifampicin, suggesting that relatively brief exposures to a critical concentration of rifampicin are sufficient to kill intermittently metabolising mycobacterial populations. The high protein binding of rifapentine (97%) may explain the suboptimal efficacy of the currently recommended dose of this drug.

The toxicity of rifampicin is related to dose and administration interval, with increasing rates of presumed hypersensitivity with higher doses combined with administration frequency of once weekly or less. Rifabutin toxicity is related to dose and concomitant use of CYP3A inhibitors.

The rifamycins illustrate the complexity of predicting the pharmacodynamics of treatment of an intracellular pathogen with the capacity for dormancy.

Copyright information

© Adis International Limited 2001

Authors and Affiliations

  • William J. Burman
    • 1
  • Keith Gallicano
    • 2
  • Charles Peloquin
    • 3
  1. 1.Department of Public Health, Denver Health and Hospital Authority and the Department of Medicine (Division of Infectious Diseases)University of Colorado Health Sciences CenterDenverUSA
  2. 2.Clinical Investigational UnitOttawa General HospitalOttawaCanada
  3. 3.Infectious Diseases Pharmacokinetics LaboratoryNational Jewish CenterDenverUSA
  4. 4.DenverUSA