title: P-glycoprotein mediated drug interactions in animals and humans with cancer.
abstract: 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.
authors.affiliation: Program in Individualized Medicine (PrIMe), Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA.
authors.forename: K L
authors.initials: KL
authors.lastname: Mealey
authors.forename: J
authors.initials: J
authors.lastname: Fidel
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D004347:Drug Interactions; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents
keywords: ABCB1; Chemotherapy; Doxorubicin vincristine; Drug Interaction; Ketoconazole; MDR1; Oncology; Spinosad