Effects of food on the clinical pharmacokinetics of anticancer agents: underlying mechanisms and implications for oral chemotherapy

Abstract

Pharmacokinetic interactions between food and orally administered drugs involve changes mainly in the absorption and metabolism of a drug, and may have clinical implications. Such interactions, in particular, may be of major clinical significance for cancer chemotherapy since the majority of anticancer agents are toxic, have a low therapeutic index and are administered long term, most often in combination with other cytotoxic agents. The purpose of this review is to compare the pharmacokinetic profiles of various anticancer drugs, including chemopreventive agents that have been examined previously in fasted and fed conditions, and to discuss the underlying basis/mechanisms of food effect in light of a drug's physicochemical and pharmacokinetic properties. Clinical pharmacokinetic parameters such as maximum concentration, area under the concentration-time curve, time to maximum concentration and half-life for each drug are compared in fasted and fed states, and specific dietary recommendations are summarised accordingly. In addition, the effects of food on the metabolite kinetics and pharmacodynamic responses, and the potential role of food effect in the modulation of oral biovariability and multidrug resistance have been extensively discussed. Overall, this comprehensive pharmacokinetic analysis indicates that a broad spectrum of food effects is seen among anticancer agents because of diverse factors regulating each drug's oral bioavailability and its interactions with food. The consideration of such effects is important, as it could lead to more rational pharmacological monitoring and possibly improve the oral chemotherapy of cancer in children, adults and the elderly.