| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Review |
Departments of
1
Pathology and
2
Biochemistry, University of Louisville School of Medicine, Louisville, KY 40292.
a Address correspondence to this author at: Department of Pathology, University of Louisville, Louisville, KY 40292. Fax 502-852-1771; e-mail ROVALDO1{at}ULKYVM.Louisville.edu
Pharmacogenetics is the study of the linkage between an individual's genotype and that individual's ability to metabolize a foreign compound. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Phenotypes exhibiting poor and ultraextensive metabolism result from genetic variance (polymorphism) of enzymes involved in metabolism. Thus, in pharmacogenetic studies one applies genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug metabolism phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic efficiency. More than 25 commonly prescribed medicines are metabolized by the cytochrome P-4502D6 (CYP2D6) isoenzyme, and polymorphism of the CYP2D6 gene affects the therapeutic management of up to 17% of individuals in some ethnic groups. In this review, we summarize and update information concerning drug-metabolizing genotypes with emphasis on CYP2D6 genotyping techniques that can be applied by the clinical laboratory for linking human genetics to therapeutic management.
Key Words: indexing terms: cytochrome P-450 • drug metabolism • human genetics • outcomes research • preventive medicine • therapeutic drug monitoring • tricyclic antidepressants
The following articles in journals at HighWire Press have cited this article:
|
|
 |
|
  R. Valdes Jr and M. W. Linder Fine-Tuning Pharmacogenetics: Paradigm for Linking Laboratory Results to Clinical Action Clin. Chem., September 1, 2004; 50(9): 1498 - 1499. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Iohom, D. Fitzgerald, and A. J. Cunningham Principles of pharmacogenetics--implications for the anaesthetist Br. J. Anaesth., September 1, 2004; 93(3): 440 - 450. [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Bjornsson, J. T. Callaghan, H. J. Einolf, V. Fischer, L. Gan, S. Grimm, J. Kao, S. P. King, G. Miwa, L. Ni, et al. THE CONDUCT OF IN VITRO AND IN VIVO DRUG-DRUG INTERACTION STUDIES: A PHARMACEUTICAL RESEARCH AND MANUFACTURERS OF AMERICA (PhRMA) PERSPECTIVE Drug Metab. Dispos., July 1, 2003; 31(7): 815 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Bjornsson, J. T. Callaghan, H. J. Einolf, V. Fischer, L. Gan, S. Grimm, J. Kao, S. P. King, G. Miwa, L. Ni, et al. The Conduct of In Vitro and In Vivo Drug-Drug Interaction Studies: A PhRMA Perspective J. Clin. Pharmacol., May 1, 2003; 43(5): 443 - 469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ji, S. Pan, J. Marti-Jaun, E. Hanseler, K. Rentsch, and M. Hersberger Single-Step Assays to Analyze CYP2D6 Gene Polymorphisms in Asians: Allele Frequencies and a Novel *14B Allele in Mainland Chinese Clin. Chem., July 1, 2002; 48(7): 983 - 988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Claassen, N. Pascoe, A. F. Schatzberg, and G. M. Murphy Jr Rapid Detection of the C-1496G Polymorphism in the CYP2D6 *2 Allele Clin. Chem., December 1, 2001; 47(12): 2153 - 2155. [Full Text] [PDF]
|
|
|
|
|
|
M. M. Shi, M. R. Bleavins, and F. A. de la Iglesia Pharmacogenetic Application in Drug Development and Clinical Trials Drug Metab. Dispos., April 1, 2001; 29(4): 591 - 595. [Abstract] [Full Text]
|
|
|
|
|
|
S. A. Cavalli, M. H. Hirata, and R. D.C. Hirata Detection of MboII Polymorphism at the 5' Promoter Region of CYP3A4, Clin. Chem., February 1, 2001; 47(2): 348 - 351. [Full Text] [PDF]
|
|
|
|
|
|
M. Nauck, U. Stein, S. von Karger, W. Marz, and H. Wieland Rapid Detection of the C3435T Polymorphism of Multidrug Resistance Gene 1 Using Fluorogenic Hybridization Probes Clin. Chem., December 1, 2000; 46(12): 1995 - 1997. [Full Text] [PDF]
|
|
|
|
|
|
M. Hersberger, J. Marti-Jaun, K. Rentsch, and E. Hanseler Rapid Detection of the CYP2D6*3, CYP2D6*4, and CYP2D6*6 Alleles by Tetra-Primer PCR and of the CYP2D6*5 Allele by Multiplex Long PCR Clin. Chem., August 1, 2000; 46(8): 1072 - 1077. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Hirth, P. B. Watkins, M. Strawderman, A. Schott, R. Bruno, and L. H. Baker The Effect of an Individual's Cytochrome CYP3A4 Activity on Docetaxel Clearance Clin. Cancer Res., April 1, 2000; 6(4): 1255 - 1258. [Abstract] [Full Text]
|
|
|
|
 |
|
 Understanding the Cytochrome P450 Isoenzyme System Journal Watch Psychiatry, July 1, 1999; 1999(701): 19 - 19. [Full Text]
|
|
|
|
|
|
M. W. Linder and P. E. Keck Jr. Standards of laboratory practice: antidepressant drug monitoring Clin. Chem., May 1, 1998; 44(5): 1073 - 1084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sugiuchi, T. Irie, Y. Uji, T. Ueno, T. Chaen, K. Uekama, and H. Okabe Homogeneous assay for measuring low-density lipoprotein cholesterol in serum with triblock copolymer and {alpha}-cyclodextrin sulfate Clin. Chem., March 1, 1998; 44(3): 522 - 531. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
