Details

Autor(en) / Beteiligte

• Marchetti, Serena
• Mazzanti, Roberto
• Beijnen, Jos H.
• Schellens, Jan H. M.

Titel

Concise Review: Clinical Relevance of Drug–Drug and Herb–Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P‐glycoprotein)

Ist Teil von

• The oncologist (Dayton, Ohio), 2007-08, Vol.12 (8), p.927-941

Ort / Verlag

Durham, NC, USA: AlphaMed Press

Erscheinungsjahr

2007

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Learning Objectives After completing this course, the reader will be able to: Identify important sources of variability in drug exposure caused by drug interactions mediated by P‐glycoprotein. Describe how unwanted drug–drug interactions may lead to unexpected serious toxicity or undertreatment. Prevent these interactions by individualizing pharmacotherapy; this means selecting noninteracting drugs or adapting the dose of (the) interacting drug(s). Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com The importance of P‐glycoprotein (P‐gp) in drug–drug interactions is increasingly being identified. P‐gp has been reported to affect the pharmacokinetics of numerous structurally and pharmacologically diverse substrate drugs. Furthermore, genetic variability in the multidrug resistance 1 gene influences absorption and tissue distribution of drugs transported. Inhibition or induction of P‐gp by coadministered drugs or food as well as herbal constituents may result in pharmacokinetic interactions leading to unexpected toxicities or undertreatment. On the other hand, modulation of P‐gp expression and/or activity may be a useful strategy to improve the pharmacological profile of anticancer P‐gp substrate drugs. In recent years, the use of complementary and alternative medicine (CAM), like herbs, food, and vitamins, by cancer patients has increased significantly. CAM use substantially increases the risk for interactions with anticancer drugs, especially because of the narrow therapeutic window of these compounds. However, for most CAMs, it is unknown whether they affect metabolizing enzymes and/or drug transporter activity. Clinically relevant interactions are reported between St John's wort or grapefruit juice and anticancer as well as nonanticancer drugs. CAM–drug interactions could explain, at least in part, the large interindividual variation in efficacy and toxicity associated with drug therapy in both cancer and noncancer patients. The study of drug–drug, food–drug, and herb–drug interactions and of genetic factors affecting pharmacokinetics and pharmacodynamics is expected to improve drug safety and will enable individualized drug therapy. Disclosure of potential conflicts of interest is found at the end of this article.