| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Clinical Pharmacology: Concise Drug Reviews |
aDivision of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; bDepartment of Internal Medicine, Postgraduate School in Oncology, University of Florence, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; cUtrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands
Key Words. P-glycoprotein • Drug interaction • Complementary and alternative medicine • CAM • Pharmacokinetics Pharmacodynamics
Correspondence: Jan H. M. Schellens, M.D., Ph.D., The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Telephone: +31-20-512-2446; Fax: +31-20-512-2572; e-mail: jhm{at}nki.nl
Received February 12, 2007; accepted for publication May 29, 2007.
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.
This article has been cited by other articles:
 |
|
 |
|
  S. S. Shord, K. Shah, and A. Lukose Drug--Botanical Interactions: A Review of the Laboratory, Animal, and Human Data for 8 Common Botanicals Integr Cancer Ther, September 1, 2009; 8(3): 208 - 227. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Munshi, L. H. Ni, and M. S. Tiwana Complementary and Alternative Medicine in Present Day Oncology Care: Promises and Pitfalls Jpn. J. Clin. Oncol., August 5, 2008; (2008) hyn066v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Miller, B. Bauer, and A. M. S. Hartz Modulation of P-Glycoprotein at the Blood-Brain Barrier: Opportunities to Improve Central Nervous System Pharmacotherapy Pharmacol. Rev., June 1, 2008; 60(2): 196 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Liu, C. Chen, and B. J. Smith Progress in Brain Penetration Evaluation in Drug Discovery and Development J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 349 - 356. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | CONTACT US | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| THE ONCOLOGIST | STEM CELLS | CME | ALPHAMED PRESS JOURNALS |
