Antineoplastic agents. Drug interactions of clinical significance.

With the use of numerous drugs in the treatment of cancer, the potential for drug interactions is considerable. Because of the limited therapeutic indices of anticancer drugs, one should be aware that even small alterations in pharmacokinetics or pharmacodynamics may result in serious adverse effects. Pharmacokinetic drug interactions may alter absorption, bioavailability, distribution, metabolism and elimination patterns. For example, allopurinol inhibits the enzyme xanthine oxidase, thereby blocking the first-pass metabolism of mercaptopurine. Due to this drug interaction, plasma concentrations of mercaptopurine can increase up to 5-fold. Pharmacodynamic drug interactions are characterised by a similar or opposing pharmacological effect of both drugs upon the same biological system. For example, cotrimoxazole (trimethoprim-sulfamethoxazole) inhibits folic acid metabolism through direct binding to dihydrofolate reductase, an enzyme which is also inhibited by methotrexate. More pharmacological investigations are needed to understand the mechanisms and clinical implications of drug interactions with antineoplastic agents.