Pharmacokinetics and pharmacodynamics of drug interactions involving rifampicin, rifabutin and antimalarial drugs

Malaria and tuberculosis (TB) are two major global diseases mostly affecting the developing countries. Their treatment is often complex because of the drugs used, multidrug resistance, drug interactions and logistic problems such as drug availability and access. Patients are treated for TB for a minimum of 6 months and may concomitantly develop and be treated for malaria, especially during the rainy season. Rifampicin, a standard component of combination regimens for treating TB, is a potent inducer of hepatic cytochrome and other metabolic enzymes and is able to influence the pharmacokinetics of many drugs. Rifabutin, another rifamycin used less frequently than rifampicin, can also interact with drugs metabolized through the hepatic cytochromes. The mechanisms of any interaction of rifamycins with drugs used in malaria are not well defined. To complicate matters, acute malaria also plays a role in the pharmacokinetics and pharmacodynamics of drugs (i.e. quinine). The aim of this paper is to review known and potential drug-drug interactions between rifampicin, rifabutin and antimalarial drugs.