This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kaiser, R. Articles by Brockmöller, J. Search for Related Content PubMed PubMed Citation Articles by Kaiser, R. Articles by Brockmöller, J. Social Bookmarking                            What's this?

Patient-Tailored Antiemetic Treatment With 5-Hydroxytryptamine Type 3 Receptor Antagonists According to Cytochrome P-450 2D6 Genotypes

From the Institute of Clinical Pharmacology and Department of Hematology and Oncology, University Medical Center Charité, Humboldt University of Berlin, Berlin, and Department of Clinical Pharmacology, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany.

Address reprint requests to Rolf Kaiser, MD, Abteilung für Klinische Pharmakologie, Universitätsklinikum der Georg-August-Universität Göttingen, Robert Koch Str 40, D-37075 Göttingen, Germany: email: rolf.kaiser{at}med.uni-goettingen.de

PURPOSE: The use of serotonin 5-hydroxytryptamine type 3 receptor antagonists has substantially reduced, but not eliminated, nausea and vomiting in cancer chemotherapy. This study sought to investigate whether efficacy of antiemetic treatment with ondansetron and tropisetron depends on cytochrome P-450 2D6 (CYP2D6) genotype, hypothesizing that the rapid and particularly the ultrarapid metabolizers of these drugs are at risk of being undertreated.

PATIENTS AND METHODS: Included in the study were 270 cancer patients receiving their first day of chemotherapy. Nausea and vomiting were documented using standardized interviews. The intensity of nausea was measured with visual analog scales before and twice during the chemotherapy. The relationship between the CYP2D6 genotypes and the tropisetron serum concentrations 3 and 6 hours after drug administration was analyzed in a subgroup of 42 patients. CYP2D6 genotyping was carried out by polymerase chain reaction–restriction fragment length polymorphism analysis.

RESULTS: Genetically defined poor metabolizers had higher serum concentrations of tropisetron than all other patients (P < .03). Approximately 30% of all patients receiving chemotherapy experienced nausea and vomiting. Genetically defined ultrarapid meta-bolizers of CYP2D6 substrates had higher frequency of vomiting within the first 4 hours (P < .001) and within the period 5 to 24 hours (P < .03) after treatment than all the other patients; the tendency for nausea was similar. This difference was more pronounced in patients treated with tropisetron than in those treated with ondansetron.

CONCLUSION: Antiemetic treatment with tropisetron or ondansetron could be improved by adjustment for the CYP2D6 genotype; approximately 50 subjects would have to be genotyped to protect one patient from severe emesis.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. Nielsen and N.V. Olsen Genetic polymorphisms in the cytochrome P450 system and efficacy of 5-hydroxytryptamine type 3 receptor antagonists for postoperative nausea and vomiting Br. J. Anaesth., October 1, 2008; 101(4): 441 - 445. [Full Text] [PDF]

				D. Buchanan and K. Muirhead Letter to the editor: Use Intractable nausea and vomiting successfully related with granisetron 5-hydroxtrytamine type 3 receptor antagonists in Palliative Medicine Palliative Medicine, December 1, 2007; 21(8): 725 - 726. [PDF]

				A. Georgy, J. Neceskas, and S. Goodin Antiemetic care for patients with breast cancer: Focus on drug interactions and safety concerns Am. J. Health Syst. Pharm., November 1, 2007; 64(21): 2227 - 2236. [Abstract] [Full Text] [PDF]

				Amal Al Omari and D. J. Murry Pharmacogenetics of the Cytochrome P450 Enzyme System: Review of Current Knowledge and Clinical Significance Journal of Pharmacy Practice, June 1, 2007; 20(3): 206 - 218. [Abstract] [PDF]

				K. A. Candiotti, F. Nhuch, A. Kamat, K. Deepika, K. L. Arheart, D. J. Birnbach, and D. A. Lubarsky Granisetron Versus Ondansetron Treatment for Breakthrough Postoperative Nausea and Vomiting After Prophylactic Ondansetron Failure: A Pilot Study Anesth. Analg., June 1, 2007; 104(6): 1370 - 1373. [Abstract] [Full Text] [PDF]

				D. E. Feierman, G. Trunfio, A. Morankar, and E. Kharasch More than Polymorphism Anesth. Analg., June 1, 2007; 104(6): 1605 - 1605. [Full Text] [PDF]

				P. K. Janicki More than Polymorphism Anesth. Analg., June 1, 2007; 104(6): 1605 - 1606. [Full Text] [PDF]

				G. H. Wynn, N. B. Sandson, and K. L. Cozza Gastrointestinal Medications Psychosomatics, February 1, 2007; 48(1): 79 - 85. [Abstract] [Full Text] [PDF]

				S. J. Gardiner and E. J. Begg Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice Pharmacol. Rev., September 1, 2006; 58(3): 521 - 590. [Abstract] [Full Text] [PDF]

				T. J. Gan Risk factors for postoperative nausea and vomiting. Anesth. Analg., June 1, 2006; 102(6): 1884 - 1898. [Abstract] [Full Text] [PDF]

				P. K. Janicki, H. G. Schuler, T. M. Jarzembowski, and M. Rossi II Prevention of Postoperative Nausea and Vomiting with Granisetron and Dolasetron in Relation to CYP2D6 Genotype. Anesth. Analg., April 1, 2006; 102(4): 1127 - 1133. [Abstract] [Full Text] [PDF]

				S. Bernard, K. A. Neville, A. T. Nguyen, and D. A. Flockhart Interethnic Differences in Genetic Polymorphisms of CYP2D6 in the U.S. Population: Clinical Implications. Oncologist, February 1, 2006; 11(2): 126 - 135. [Abstract] [Full Text] [PDF]

				M. Ingelman-Sundberg and C. Rodriguez-Antona Pharmacogenetics of drug-metabolizing enzymes: implications for a safer and more effective drug therapy Phil Trans R Soc B, August 29, 2005; 360(1460): 1563 - 1570. [Abstract] [Full Text] [PDF]

				R. R Shah Pharmacogenetics in drug regulation: promise, potential and pitfalls Phil Trans R Soc B, August 29, 2005; 360(1460): 1617 - 1638. [Abstract] [Full Text] [PDF]

				M. Aapro Granisetron: An Update on its Clinical Use in the Management of Nausea and Vomiting Oncologist, November 1, 2004; 9(6): 673 - 686. [Abstract] [Full Text] [PDF]

				A. J Coop Comment: electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine-3 receptor antagonists Ann. Pharmacother., December 1, 2003; 37(12): 1918 - 1918. [Full Text] [PDF]

				A. L. Kovac Is There Rationale to Use an Antiemetic in the Same Class for the Treatment of Patients Who Experience Postoperative Nausea and Vomiting Despite Prophylaxis? Anesth. Analg., December 1, 2003; 97(6): 1857 - 1857. [Full Text] [PDF]

				P.-B. Tremblay, R. Kaiser, O. Sezer, N. Rosler, C. Schelenz, K. Possinger, I. Roots, and J. Brockmoller Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients J. Clin. Oncol., June 1, 2003; 21(11): 2147 - 2155. [Abstract] [Full Text] [PDF]

				F. M. Schnell Chemotherapy-Induced Nausea and Vomiting: The Importance of Acute Antiemetic Control Oncologist, April 1, 2003; 8(2): 187 - 198. [Abstract] [Full Text] [PDF]

				H. L. McLeod Genetic Strategies to Individualize Supportive Care J. Clin. Oncol., June 15, 2002; 20(12): 2765 - 2767. [Full Text] [PDF]