P-Glycoprotein Mediated Drug Interactions in Animals and Humans with Cancer

Drug-drug interactions can cause unanticipated patient morbidity and mortality. The consequences of drug- drug interactions can be especially severe when anticancer drugs are involved because of their narrow therapeutic index. Veterinary clinicians have traditionally been taught that drug- drug interactions result from alterations in drug metabolism, renal excretion or protein binding. More recently, drug- drug interactions resulting from inhibition of P- glycoprotein- mediated drug transport have been identified in both human and veterinary patients. Many drugs commonly used in veterinary patients are capable of inhibiting P- glycoprotein function and thereby causing an interaction that results in severe chemotherapeutic drug toxicity. The intent of this review is to describe the mechanism and clinical implications of drug- drug interactions involving P- glycoprotein and anticancer drugs. Equipped with this information, veterinarians can prevent serious drug- drug interactions by selecting alternate drugs or adjusting the dose of interacting drugs.