There is renewed interest in the rifamycins, primarily from evidence that higher doses than have been previously used may allow a markedly shortened treatment of active and latent tuberculosis (TB). We review recent studies of the pharmacokinetics, pharmacodynamics and pharmacogenomics of rifampicin, rifapentine and rifabutin. The rifamycins have complex metabolic pathways and, therefore, have wide interpatient variability in drug exposure (10-fold or greater). Some of the reasons for the broad range in rifamycin exposure are now being elucidated: body weight, disease state, ingestion with food and polymorphisms in genes for drug transporter proteins. Children require 2-to 3-fold higher doses of rifampicin and rifapentine than adults do. Greater rifamycin exposure is closely correlated with bactericidal and sterilizing activities in the mouse model of TB treatment. The use of high-dose rifampicin and daily rifapentine allows treatment to be shortened to 3 months in the mouse model, and clinical trials are under way to evaluate these regimens in humans. Little is known about the relationship between rifamycin dose and toxicity, when daily dosing is used. New ways of using an old drug class-the rifamycins-may markedly improve TB treatment yet again.
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Pharmacology, Toxicology and Pharmaceutics(all)