P-glycoprotein mediated drug interactions in animals and humans with cancer

J Vet Intern Med. 2015 Jan;29(1):1-6. doi: 10.1111/jvim.12525.

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.

Keywords: ABCB1; Chemotherapy; Doxorubicin vincristine; Drug Interaction; Ketoconazole; MDR1; Oncology; Spinosad.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / pharmacokinetics*
  • Drug Interactions
  • Humans
  • Neoplasms / drug therapy*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents