This Article Full Text Full Text (PDF) eLetters: Submit a response to this article Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services E-mail this article link to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints/Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kruijtzer, C.M.F. Articles by Schellens, J.H.M. Search for Related Content PubMed PubMed Citation Articles by Kruijtzer, C.M.F. Articles by Schellens, J.H.M.

Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview

^a Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; ^b Department of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands; ^c Division of Drug Toxicology, Faculty of Pharmacy, Utrecht University, Utrecht, The Netherlands; ^d Department of Experimental Therapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Correspondence: J.H.M. Schellens, M.D., Ph.D., The Netherlands Cancer Institute/Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Telephone: 31-0-20-5122569; Fax: 31-0-20-5122572; e-mail: jhm{at}nki.nl

The oral bioavailability of many cytotoxic drugs is low and/or highly variable. This can be caused by high affinity for drug transporters and activity of metabolic enzymes in the gastrointestinal tract and liver. In this review, we will describe the main involved drug transporters and metabolic enzymes and discuss novel methods to improve oral treatment of affected substrate drugs. Results of preclinical and clinical phase I and II studies will be discussed in which affected substrate drugs, such as paclitaxel, docetaxel, and topotecan, are given orally in combination with an inhibitor of drug transport or drug metabolism. Future randomized studies will, hopefully, confirm that this strategy for oral treatment is at least as equally effective and safe as standard intravenous administration of these drugs.

Key Words. Cytochrome P450 • Drug transporters • Oral chemotherapy • Pharmacokinetics

This article has been cited by other articles:

				S. Marchetti, R. Mazzanti, J. H. Beijnen, and J. H. M. Schellens Concise Review: Clinical Relevance of Drug Drug and Herb Drug Interactions Mediated by the ABC Transporter ABCB1 (MDR1, P-glycoprotein) Oncologist, August 1, 2007; 12(8): 927 - 941. [Abstract] [Full Text] [PDF]

				C. Q. Xia, N. Liu, G. T. Miwa, and L.-S. Gan Interactions of Cyclosporin A with Breast Cancer Resistance Protein Drug Metab. Dispos., April 1, 2007; 35(4): 576 - 582. [Abstract] [Full Text] [PDF]

				J. Meletiadis, S. Chanock, and T. J. Walsh Human Pharmacogenomic Variations and Their Implications for Antifungal Efficacy Clin. Microbiol. Rev., October 1, 2006; 19(4): 763 - 787. [Abstract] [Full Text] [PDF]

				C. Q. Xia, N. Liu, D. Yang, G. Miwa, and L.-S. Gan EXPRESSION, LOCALIZATION, AND FUNCTIONAL CHARACTERISTICS OF BREAST CANCER RESISTANCE PROTEIN IN CACO-2 CELLS Drug Metab. Dispos., May 1, 2005; 33(5): 637 - 643. [Abstract] [Full Text] [PDF]

				J. H. M. Schellens ABC transporters and cancer treatment AACR Meeting Abstracts, April 1, 2005; 2005(1): 1476 - 1477. [Abstract]

				H. Burger, H. van Tol, A. W. M. Boersma, M. Brok, E. A. C. Wiemer, G. Stoter, and K. Nooter Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump Blood, November 1, 2004; 104(9): 2940 - 2942. [Abstract] [Full Text] [PDF]

				A. Sparreboom, M. C. Cox, M. R. Acharya, and W. D. Figg Herbal Remedies in the United States: Potential Adverse Interactions With Anticancer Agents J. Clin. Oncol., June 15, 2004; 22(12): 2489 - 2503. [Abstract] [Full Text] [PDF]

				Y. Kimura, Y. Nagata, and R. K. Buddington Some Dietary Fibers Increase Elimination of Orally Administered Polychlorinated Biphenyls but Not That of Retinol in Mice J. Nutr., January 1, 2004; 134(1): 135 - 142. [Abstract] [Full Text] [PDF]