JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2012, 61(3):115-126

Phenotyping of enzymes participating in drug metabolism

Svatopluk Světlík*, Karolína Hronová, Ondřej Slanař
Univerzita Karlova v Praze, 1. lékařská fakulta, Farmakologický ústav

Pharmacogenetics is a rapidly developing field of science promising individualization of treatment through determination of genetic polymorphism in pharmacodynamics (receptors and other drug targets) and pharmacokinetics (carriers, metabolic enzymes). Enzyme activity may be predicted using genotyping or directly phenotyped - after administration of a probe substrate. This review article deals with some important metabolic enzyme polymorphisms and their phenotyping methods. Special consideration is given to the analytical methods described in the literature, which can be used to determine the metabolic rate.

Keywords: pharmacogenetics; cytochrome P450; HPLC; drug biotransformation

Received: April 16, 2012; Accepted: May 17, 2012; Published: March 1, 2012  Show citation

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Světlík S, Hronová K, Slanař O. Phenotyping of enzymes participating in drug metabolism. Čes. slov. farm. 2012;61(3):115-126.
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    References

    1. Gardiner S. J., Begg E. J.: Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev. 2006; 58, 521-590. Go to original source... Go to PubMed...
    2. Hoskins J. M., Marcuello E., Altes A., Marsh S., Maxwell T., van Booven D. J., Pare L., Culverhouse R., McLeod H. L., Baiget M.: Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Clin Cancer Res. 2008; 14, 1788-1796. Go to original source... Go to PubMed...
    3. Bond G. L., Hu W., Levine A.: A single nucleotide polymorphism in the MDM2 gene: from a molecular and cellular explanation to clinical effect. Cancer Res. 2005; 65, 5481-5484. Go to original source... Go to PubMed...
    4. Hayashi K.: PCR-SSCP: a simple and sensitive method for detection of mutations in the genomic DNA. PCR Methods Appl. 1991; 1, 34-38. Go to original source... Go to PubMed...
    5. Nelson D. R.: The cytochrome p450 homepage. Hum Genomics. 2009; 4, 59-65. Go to original source... Go to PubMed...
    6. Hukkanen J.: Xenobiotic-metabolizing cytochrome P450 enzymes in human lung. Oulu: University of Oulu 2000; 69 s.
    7. Eichelbaum M., Ingelman-Sundberg M., Evans W. E.: Pharmacogenomics and individualized drug therapy. Annu Rev Med. 2006; 57, 119-137. Go to original source... Go to PubMed...
    8. Ingelman-Sundberg M., Sim S. C., Gomez A., Rodriguez-Antona C.: Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects. Pharmacol Ther. 2007; 116, 496-526. Go to original source... Go to PubMed...
    9. Zanger U. M., Raimundo S., Eichelbaum M.: Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol. 2004; 369, 23-37. Go to original source... Go to PubMed...
    10. Kirchheiner J., Brockmoller J.: Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin Pharmacol Ther. 2005; 77, 1-16. Go to original source... Go to PubMed...
    11. Anzenbacher P., Anzenbacherova E.: Cytochromes P450 and metabolism of xenobiotics. Cell Mol Life Sci. 2001; 58, 737-747. Go to original source... Go to PubMed...
    12. Buzkova H., Pechandova K., Slanar O., Perlik F.: Frequency of single nucleotide polymorphisms of CYP2D6 in the Czech population. Cell Biochem Funct. 2008; 26, 76-81. Go to original source... Go to PubMed...
    13. Abdel-Rahman S. M., Leeder J. S., Wilson J. T., Gaedigk A., Gotschall R. R., Medve R., Liao S., Spielberg S. P., Kearns G. L.: Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation. J Clin Pharmacol. 2002; 42, 24-29. Go to original source... Go to PubMed...
    14. Subrahmanyam V., Renwick A. B., Walters D. G., Young P. J., Price R. J., Tonelli A. P., Lake B. G.: Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos. 2001; 29, 1146-1155.
    15. Johnson J. A., Burlew B. S.: Metoprolol metabolism via cytochrome P4502D6 in ethnic populations. Drug Metab Dispos. 1996; 24, 350-355. Go to original source...
    16. Schmid B., Bircher J., Preisig R., Kupfer A.: Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther. 1985; 38, 618-624. Go to original source... Go to PubMed...
    17. Draft FDA guidance for industry.
    18. Streetman D. S., Ellis R. E., Nafziger A. N., Leeder J. S., Gaedigk A., Gotschall R., Kearns G. L., Bertino J. S. Jr.: Dose dependency of dextromethorphan for cytochrome P450 2D6 (CYP2D6. phenotyping. Clin Pharmacol Ther. 1999; 66, 535-541. Go to original source... Go to PubMed...
    19. Frank D., Jaehde U., Fuhr U.: Evaluation of probe drugs and pharmacokinetic metrics for CYP2D6 phenotyping. Eur J Clin Pharmacol. 2007; 63, 321-333. Go to original source... Go to PubMed...
    20. Duche J. C., Querol-Ferrer V., Barre J., Mesangeau M., Tillement J. P.: Dextromethorphan O-demethylation and dextrorphan glucuronidation in a French population. Int J Clin Pharmacol Ther Toxicol. 1993; 31, 392-398.
    21. Hu O. Y., Tang H. S., Lane H. Y., Chang W. H., Hu T. M.: Novel single-point plasma or saliva dextromethorphan method for determining CYP2D6 activity. J Pharmacol Exp Ther. 1998; 285, 955-960. Go to original source...
    22. Jacqz E., Dulac H., Mathieu H.: Phenotyping polymorphic drug metabolism in the French Caucasian population. Eur J Clin Pharmacol. 1988; 35, 167-171. Go to original source... Go to PubMed...
    23. Chladek J., Zimova G., Martinkova J., Tuma I.: Intraindividual variability and influence of urine collection period on dextromethorphan metabolic ratios in healthy subjects. Fundam Clin Pharmacol Ther. 1999; 508-515. Go to original source... Go to PubMed...
    24. Hoskins J. M., Shenfield G. M., Gross A. S.: Modified high-performance liquid chromatographic method to measure both dextromethorphan and proguanil for oxidative phenotyping. J Chromatogr B Biomed Sci Appl. 1997; 696, 81-87. Go to original source... Go to PubMed...
    25. Daali Y., Cherkaoui S., Doffey-Lazeyras F., Dayer P., Desmeules J. A.: Development and validation of a chemical hydrolysis method for dextromethorphan and dextrophan determination in urine samples: application to the assessment of CYP2D6 activity in fibromyalgia patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2008; 861, 56-63. Go to original source... Go to PubMed...
    26. Kohler D., Hartter S., Fuchs K., Sieghart W., Hiemke C.: CYP2D6 genotype and phenotyping by determination of dextromethorphan and metabolites in serum of healthy controls and of patients under psychotropic medication. Pharmacogenetics. 1997; 7, 453-461. Go to original source... Go to PubMed...
    27. Borges S., Li L., Hamman M. A., Jones D. R., Hall S. D., Gorski J. C.: Dextromethorphan to dextrorphan urinary metabolic ratio does not reflect dextromethorphan oral clearance. Drug Metab Dispos. 2005; 33, 1052-1055. Go to original source... Go to PubMed...
    28. Tamminga W. J., Wemer J., Oosterhuis B., Brakenhoff J. P., Gerrits M. G., de Zeeuw R. A., de LeijL. F., Jonkman J. H.: An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19. Eur J Clin Pharmacol. 2001; 57, 143-146. Go to original source... Go to PubMed...
    29. Hou Z. Y., Pickle L. W., Meyer P. S., Woosley R. L.: Salivary analysis for determination of dextromethorphan metabolic phenotype. Clin Pharmacol Ther. 1991; 49, 410-419. Go to original source... Go to PubMed...
    30. Park Y. H., Kullberg M. P., Hinsvark O. N.: Quantitative determination of dextromethorphan and three metabolites in urine by reverse-phase high-performance liquid chromatography. J Pharm Sci. 1984; 73, 24-29. Go to original source... Go to PubMed...
    31. Kim E. M., Lee J. S., Park M. J., Choi S. K., Lim M. A., Chung H. S.: Standardization of method for the analysis of dextromethorphan in urine. Forensic Sci Int. 2006; 161, 198-201. Go to original source... Go to PubMed...
    32. Rodrigues W. C., Wang G., Moore C., Agrawal A., Vincent M. J., Soares J. R.: Development and validation of ELISA and GC-MS procedures for the quantification of dextromethorphan and its main metabolite dextrorphan in urine and oral fluid. J Anal Toxicol. 2008; 32, 220-226. Go to original source... Go to PubMed...
    33. Ducharme J., Abdullah S., Wainer I. W.: Dextromethorphan as an in vivo probe for the simultaneous determination of CYP2D6 and CYP3A activity. J Chromatogr B Biomed Appl. 1996; 678, 113-128. Go to original source... Go to PubMed...
    34. Vengurlekar S. S., Heitkamp J., McCush F., Velagaleti P. R., Brisson J. H., Bramer S. L.: A sensitive LC-MS/MS assay for the determination of dextromethorphan and metabolites in human urine-application for drug interaction studies assessing potential CYP3A and CYP2D6 inhibition. J Pharm Biomed Anal. 2002; 30, 113-124. Go to original source... Go to PubMed...
    35. Chen Z. R., Somogyi A. A., Bochner F.: Simultaneous determination of dextromethorphan and three metabolites in plasma and urine using high-performance liquid chromatography with application to their disposition in man. Ther Drug Monit. 1990; 12, 97-104. Go to original source... Go to PubMed...
    36. East T., Dye D.: Determination of dextromethorphan and metabolites in human plasma and urine by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1985; 338, 99-112. Go to original source... Go to PubMed...
    37. Lin S. Y., Chen C. H., Ho H. O., Chen H. H., Sheu, M. T.: Simultaneous analysis of dextromethorphan and its three metabolites in human plasma using an improved HPLC method with fluorometric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 859, 141-146. Go to original source... Go to PubMed...
    38. Kuhlenbeck D. L., Eichold T. H., Hoke S. H., 2nd, Baker T. R., Mensen R., Wehmeyer,K. R.: On-line solid phase extraction using the Prospekt-2 coupled with a liquid chromatography/tandem mass spectrometer for the determination of dextromethorphan, dextrorphan and guaifenesin in human plasma. Eur J Mass Spectrom (Chichester, Eng.. 2005; 11, 199-208. Go to original source... Go to PubMed...
    39. Bagheri H., Es-haghi A., Rouini M. R.: Sol-gel-based solid-phase microextraction and gas chromatography-mass spectrometry determination of dextromethorphan and dextrorphan in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 818, 147-157. Go to original source... Go to PubMed...
    40. Afshar M., Rouini M. R., Amini M.: Simple chromatography method for simultaneous determination of dextromethorphan and its main metabolites in human plasma with fluorimetric detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 802, 317-322. Go to original source... Go to PubMed...
    41. Liu L. L., Wang Z., Feng X. T., Gao S.: [Column switching HPLC method for determination of dextrorphan, an active metabolite of dextromethorphan, in plasma]. Yao Xue Xue Bao. 1993; 28, 374-378.
    42. Hartter S., Baier D., Dingemanse J., Ziegler G., Hiemke C.: Automated determination of dextromethorphan and its main metabolites in human plasma by high-performance liquid chromatography and column switching. Ther Drug Monit. 1996; 18, 297-303. Go to original source... Go to PubMed...
    43. Kristensen H. T.: Simultaneous determination of dextromethorphan and its metabolites in human plasma by capillary electrophoresis. J Pharm Biomed Anal. 1998; 18, 827-838. Go to original source... Go to PubMed...
    44. Lutz U., Volkel W., Lutz R. W., Lutz, W. K.: LC-MS/MS analysis of dextromethorphan metabolism in human saliva and urine to determine CYP2D6 phenotype and individual variability in N-demethylation and glucuronidation. J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 813, 217-225. Go to original source... Go to PubMed...
    45. Leeder, J. S., Pearce, R. E., Gaedigk, A., Modak, A., Rosen, D. I.: Evaluation of a [13C]-dextromethorphan breath test to assess CYP2D6 phenotype. J Clin Pharmacol. 2008; 48, 1041-1051. Go to original source... Go to PubMed...
    46. Inoue K., Yamazaki H., Imiya K., Akasaka S., Guengerich F. P., Shimada T.: Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4'-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics. 1997; 7, 103-113. Go to original source... Go to PubMed...
    47. Miners J. O., Birkett D. J.: Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998; 45, 525-538. Go to original source... Go to PubMed...
    48. Buzkova H., Pechandova K., Slanar O., Perlik F.: Genetic Polymorphism of Cytochrome CYP2C9 in the Czech population. Klin. Biochem. Metab. 2007; 15, 102-105.
    49. Rendic S., Di Carlo F. J.: Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev. 1997; 29, 413-580. Go to original source... Go to PubMed...
    50. Streetman D. S., Bertino J. S., Jr., Nafziger A. N.: Phenotyping of drug-metabolizing enzymes in adults: a review of in-vivo cytochrome P450 phenotyping probes. Pharmacogenetics. 2000; 10, 187-216. Go to original source... Go to PubMed...
    51. Kirchheiner J., Bauer S., Meineke I., Rohde W., Prang V., Meisel C., Roots I., Brockmoller J.: Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics. 2002; 12, 101-109. Go to original source... Go to PubMed...
    52. Kirchheiner J., Brockmoller J., Meineke I., Bauer S., Rohde W., Meisel C., Roots I.: Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther. 2002; 71, 286-296. Go to original source... Go to PubMed...
    53. Veronese M. E., Miners J. O., Randles D., Gregov D., Birkett D. J.: Validation of the tolbutamide metabolic ratio for population screening with use of sulfaphenazole to produce model phenotypic poor metabolizers. Clin Pharmacol Ther. 1990; 47, 403-411. Go to original source... Go to PubMed...
    54. Lee C. R., Pieper J. A., Frye R. F., Hinderliter A. L., Blaisdell J. A., Goldstein J. A.: Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans. J Clin Pharmacol. 2003; 43, 84-91. Go to original source... Go to PubMed...
    55. Hansen L. L., Brosen K.: Quantitative determination of tolbutamide and its metabolites in human plasma and urine by high-performance liquid chromatography and UV detection. Ther Drug Monit. 1999; 21, 664-671. Go to original source... Go to PubMed...
    56. Matin S. B., Rowland M.: Simultaneous determination of tolbutamide and its metabolites in biological fluids. Analytical Letters. 1973; 6, 865-876. Go to original source...
    57. Raghow G., Meyer M. C.: High-performance liquid chromatographic assay of tolbutamide and carboxytolbutamide in human plasma. J Pharm Sci. 1981; 70, 1166-1168. Go to original source... Go to PubMed...
    58. Thomas R. C., Ikeda G. J.: The metabolic fate of tolbutamide in man and in the rat. J Med Chem. 1966; 9, 507-510. Go to original source... Go to PubMed...
    59. Klaassen T., Jetter A., Tomalik-Scharte D., Kasel D., Kirchheiner J., Jaehde U., Fuhr U.: Assessment of urinary mephenytoin metrics to phenotype for CYP2C19 and CYP2B6 activity. Eur J Clin Pharmacol. 2008; 64, 387-398. Go to original source... Go to PubMed...
    60. Tamminga W. J., Wemer J., Oosterhuis B., Wieling J., Touw D. J., de Zeeuw R. A., de Leij L. F., Jonkman J. H.: Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events. Br J Clin Pharmacol. 2001; 51, 471-474. Go to original source... Go to PubMed...
    61. Britzi M., Bialer M., Arcavi L., Shachbari A., Kapitulnik T., Soback S.: Genetic polymorphism of CYP2D6 and CYP2C19 metabolism determined by phenotyping Israeli ethnic groups. Ther Drug Monit. 2000; 22, 510-516. Go to original source... Go to PubMed...
    62. Tamminga W. J., Wemer J., Oosterhuis B., Weiling J., Wilffert B., de Leij L. F., de Zeeuw, R. A., Jonkman J. H.: CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol. 1999; 55, 177-184. Go to original source... Go to PubMed...
    63. Jurima-Romet M., Goldstein J. A., LeBelle M., Aubin R. A., Foster B. C., Walop W., Rode, A.: CYP2C19 genotyping and associated mephenytoin hydroxylation polymorphism in a Canadian Inuit population. Pharmacogenetics. 1996; 6, 329-339. Go to original source... Go to PubMed...
    64. Miura M., Motoyama S., Hinai Y., Niioka T., Hayakari M., Ogawa J., Suzuki T.: Correlation between R/S enantiomer ratio of lansoprazole and CYP2C19 activity after single oral and enteral administration. Chirality. 2010; 22, 635-640. Go to original source... Go to PubMed...
    65. Panchabhai T. S., Noronha S. F., Davis S., Shinde V. M., Kshirsagar N. A., Gogtay, N. J.: Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay). BMC Clin Pharmacol. 2006; 6, 8. Go to original source... Go to PubMed...
    66. Kim M. J., Nafziger A. N., Zhang Y., Sellers E. M., Gaedigk A., Bertino J. S. Jr.: Lack of weight-based dose dependency and intraindividual variability of omeprazole for CYP2C19 phenotyping. J Clin Pharmacol. 2004; 44, 966-973. Go to original source... Go to PubMed...
    67. Hoskins J. M., Shenfield G. M., Gross A. S.: Concordance between proguanil phenotype and CYP2C19 genotype in Chinese. Eur J Clin Pharmacol. 2003; 59, 611-614. Go to original source... Go to PubMed...
    68. Kanazawa H., Okada A., Higaki M., Yokota H., Mashige F., Nakahara K.: Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype. J Pharm Biomed Anal. 2003; 30, 1817-1824. Go to original source... Go to PubMed...
    69. Kimura M., Ieiri I., Wada Y., Mamiya K., Urae A., Iimori E., Sakai T., Otsubo K., Higuchi S.: Reliability of the omeprazole hydroxylation index for CYP2C19 phenotyping: possible effect of age, liver disease and length of therapy. Br J Clin Pharmacol. 1999; 47, 115-119. Go to original source... Go to PubMed...
    70. Nolin T. D., Frye R. F.: Stereoselective determination of the CYP2C19 probe drug mephenytoin in human urine by gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 783, 265-271. Go to original source... Go to PubMed...
    71. Huang S. L., Xie H. G., Wang W., Xu Z. H., Jiang C. H., Zhou H. H.: Determination of S/R ratio of mephenytoin in human urine by chiral HPLC and ultraviolet detection and its comparison with gas chromatography. Zhongguo Yao Li Xue Bao. 1998; 19, 548-550.
    72. Wedlund P. J., Sweetman B. J., McAllister C. B., Branch R. A., Wilkinson G. R.: Direct enantiomeric resolution of mephenytoin and its N-demethylated metabolite in plasma and blood using chiral capillary gas chromatography. J Chromatogr. 1984; 307, 121-127. Go to original source... Go to PubMed...
    73. de Morais S. M., Goldstein J. A., Xie H. G., Huang S. L., Lu Y. Q., Xia H., Xiao Z. S., Ile N., Zhou H. H.: Genetic analysis of the S-mephenytoin polymorphism in a Chinese population. Clin Pharmacol Ther. 1995; 58, 404-411. Go to original source... Go to PubMed...
    74. Yao T. W., Zeng S., Wang T. W., Chen S. Q.: Phenotype analysis of cytochrome P450 2C19 in Chinese subjects with mephenytoin S/R enantiomeric ratio in urine measured by chiral GC. Biomed Chromatogr. 2001; 15, 9-13. Go to original source...
    75. Kuang T. Y., Zhang J. M., Zou A. Q., Lou Y. Q.: A chiral capillary gas chromatographic method for direct determination of enantiomers of mephenytoin in human urine. Yao Xue Xue Bao. 1993; 28, 307-311.
    76. Mo S. L., Liu Y. H., Duan W., Wei M. Q., Kanwar J. R., Zhou S. F.: Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6. Curr Drug Metab. 2009; 10, 730-753. Go to original source... Go to PubMed...
    77. Cooper T. B., Suckow R. F., Glassman A.: Determination of bupropion and its major basic metabolites in plasma by liquid chromatography with dual-wavelength ultraviolet detection. J Pharm Sci. 1984; 73, 1104-1107. Go to original source... Go to PubMed...
    78. Yeniceli D., Dogrukol-Ak D.: An LC method for the determination of bupropion and its main metabolite, hydroxybupropion in human plasma. Chromatographia. 2009; 70, 1703-1708. Go to original source...
    79. Loboz K. K., Gross A. S., Ray J., McLachlan A. J.: HPLC assay for bupropion and its major metabolites in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 823, 115-121. Go to original source... Go to PubMed...
    80. Coles R., Kharasch E. D.: Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2007; 857, 67-75. Go to original source... Go to PubMed...
    81. Borges V., Yang E., Dunn J., Henion J.: High-throughput liquid chromatography-tandem mass spectrometry determination of bupropion and its metabolites in human, mouse and rat plasma using a monolithic column. J Chromatogr B Analyt Technol Biomed Life Sci. 2004; 804, 277-287. Go to original source... Go to PubMed...
    82. Kirchheiner J., Klein C., Meineke I., Sasse J., Zanger U. M., Murdter T. E., Roots I., Brockmoller J.: Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics. 2003; 13, 619-626. Go to original source... Go to PubMed...
    83. Pechandova K., Buzkova H., Matouskova O., Perlik F., Slanar, O.: Genetic Polymorphisms of CYP2C8 in the Czech Republic. Genet Test Mol Biomarkers. 2012 Go to original source...
    84. Green H., Soderkvist P., Rosenberg P., Mirghani R. A., Rymark P., Lundqvist E. A., Peterson C.: Pharmacogenetic studies of Paclitaxel in the treatment of ovarian cancer. Basic Clin Pharmacol Toxicol. 2009; 104, 130-137. Go to original source... Go to PubMed...
    85. Dierks E. A., Stams K. R., Lim H. K., Cornelius G., Zhang H., Ball S. E.: A method for the simultaneous evaluation of the activities of seven major human drug-metabolizing cytochrome P450s using an in vitro cocktail of probe substrates and fast gradient liquid chromatography tandem mass spectrometry. Drug Metab Dispos. 2001; 29, 23-29.
    86. Green H., Vretenbrant K., Norlander B., Peterson C.: Measurement of paclitaxel and its metabolites in human plasma using liquid chromatography/ion trap mass spectrometry with a sonic spray ionization interface. Rapid Communications in Mass Spectrometry. 2006; 20, 2183-2189. Go to original source... Go to PubMed...
    87. Huizing M. T., Sparreboom A., Rosing H., van Tellingen O., Pinedo H. M., Beijnen J. H.: Quantification of paclitaxel metabolites in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995; 674, 261-268. Go to original source... Go to PubMed...
    88. Vainchtein L. D., Thijssen B., Stokvis E., Rosing H., Schellens J. H., Beijnen J. H.: A simple and sensitive assay for the quantitative analysis of paclitaxel and metabolites in human plasma using liquid chromatography/tandem mass spectrometry. Biomed Chromatogr. 2006; 20, 139-148. Go to original source... Go to PubMed...
    89. Alexander M. S., Kiser M. M., Culley T., Kern J. R., Dolan J. W., McChesney J. D., Zygmunt J., Bannister S. J.: Measurement of paclitaxel in biological matrices: high-throughput liquid chromatographic-tandem mass spectrometric quantification of paclitaxel and metabolites in human and dog plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2003; 785, 253-261. Go to original source... Go to PubMed...
    90. Mortier K. A., Renard V., Verstraete A. G., Van Gussem A., Van Belle S., Lambert W. E.: Development and validation of a liquid chromatography-tandem mass spectrometry assay for the quantification of docetaxel and paclitaxel in human plasma and oral fluid. Anal Chem. 2005; 77, 4677-4683. Go to original source... Go to PubMed...
    91. Burk O., Wojnowski L.: Cytochrome P450 3A and their regulation. Naunyn Schmiedebergs Arch Pharmacol. 2004; 369, 105-124. Go to original source... Go to PubMed...
    92. Opdam F. L., Gelderblom H., Guchelaar H. J.: Phenotyping drug disposition in oncology. Cancer Treat Rev. 2012 Go to original source... Go to PubMed...
    93. Watkins P. B., Murray S. A., Winkelman L. G., Heuman D. M., Wrighton S. A., Guzelian P. S.: Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. J Clin Invest. 1989; 83, 688-697. Go to original source... Go to PubMed...
    94. Ged C., Rouillon J. M., Pichard L., Combalbert J., Bressot N., Bories P., Michel H., Beaune P., Maurel P.: The increase in urinary excretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J Clin Pharmacol. 1989; 28, 373-387. Go to original source... Go to PubMed...
    95. Gentile D. M., Tomlinson E. S., Maggs J. L., Park B. K., Back D. J.: Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation. J Pharmacol Exp Ther. 1996; 277, 105-112. Go to original source...
    96. Green H., Skoglund K., Rommel F., Mirghani R. A., Lotfi K.: CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity. Eur J Clin Pharmacol. 2010; 66, 383-386. Go to original source... Go to PubMed...
    97. Michael M., Cullinane C., Hatzimihalis A., O'Kane C., Milner A., Booth R., Schlicht S., Clarke S. J., Francis P.: Docetaxel pharmacokinetics and its correlation with two in vivo probes for cytochrome P450 enzymes: the C(14)-erythromycin breath test and the antipyrine clearance test. Cancer Chemother Pharmacol. 2012; 69, 125-135. Go to original source... Go to PubMed...
    98. Eeckhoudt S. L., Desager J. P., Horsmans Y., De Winne A. J., Verbeeck R. K.: Sensitive assay for midazolam and its metabolite 1'-hydroxymidazolam in human plasma by capillary high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl. 1998; 710, 165-171. Go to original source... Go to PubMed...
    99. Rubio F., Miwa B. J., Garland W. A.: Determination of midazolam and two metabolites of midazolam in human plasma by gas chromatography-negative chemical-ionization mass spectrometry. J Chromatogr. 1982; 233, 157-165. Go to original source... Go to PubMed...
    100. Lehmann B., Boulieu R.: Determination of midazolam and its unconjugated 1-hydroxy metabolite in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1995; 674, 138-142. Go to original source... Go to PubMed...
    101. Martens J., Banditt P.: Simultaneous determination of midazolam and its metabolites 1-hydroxymidazolam and 4-hydroxymidazolam in human serum using gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl. 1997; 692, 95-100. Go to original source... Go to PubMed...
    102. Mastey V., Panneton A. C., Donati F., Varin F.: Determination of midazolam and two of its metabolites in human plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl. 1994; 655, 305-310. Go to original source... Go to PubMed...
    103. Link B., Haschke M., Wenk M., Krahenbuhl S.: Determination of midazolam and its hydroxy metabolites in human plasma and oral fluid by liquid chromatography/electrospray ionization ion trap tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007; 21, 1531-1540. Go to original source... Go to PubMed...
    104. Chan K., Jones R. D.: Simultaneous determination of flumazenil, midazolam and metabolites in human biological fluids by liquid chromatography. J Chromatogr. 1993; 619, 154-160. Go to original source... Go to PubMed...
    105. Jabor V. A., Coelho E. B., Dos Santos N. A., Bonato P. S., Lanchote V. L.: A highly sensitive LC-MS-MS assay for analysis of midazolam and its major metabolite in human plasma: applications to drug metabolism. J Chromatogr B Analyt Technol Biomed Life Sci. 2005; 822, 27-32. Go to original source... Go to PubMed...
    106. ter Horst P. G. J., Foudraine N. A., Cuypers G., van Dijk E. A., Oldenhof N. J. J.: Simultaneous determination of levomepromazine, midazolam and their major metabolites in human plasma by reversed-phase liquid chromatography. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 2003; 791, 389-398. Go to original source... Go to PubMed...
    107. Marquet P., Baudin O., Gaulier J. M., Lacassie E., Dupuy J. L., Francois B., Lachatre G.: Sensitive and specific determination of midazolam and 1-hydroxymidazolam in human serum by liquid chromatography-electrospray mass spectrometry. J Chromatogr B Biomed Sci Appl. 1999; 734, 137-144. Go to original source... Go to PubMed...
    108. Ha H. R., Rentsch K. M., Kneer J., Vonderschmitt D. J.: Determination of midazolam and its alpha-hydroxy metabolite in human plasma and urine by high-performance liquid chromatography. Ther Drug Monit. 1993; 15, 338-343. Go to original source... Go to PubMed...
    109. Eap C. B., Buclin T., Cucchia G., Zullino D., Hustert E., Bleiber G., Golay K. P., Aubert A. C., Baumann P., Telenti A., Kerb R.: Oral administration of a low dose of midazolam (75 mu g. as an in vivo probe for CYP3A activity). European Journal of Clinical Pharmacology. 2004; 60, 237-246. Go to original source... Go to PubMed...
    110. Walker K., Ginsberg G., Hattis D., Johns D. O., Guyton K. Z., Sonawane B.: Genetic polymorphism in N-Acetyltransferase (NAT): Population distribution of NAT1 and NAT2 activity. J Toxicol Environ Health B Crit Rev. 2009; 12, 440-472. Go to original source... Go to PubMed...
    111. Luck H., Kinzig M., Jetter A., Fuhr U., Sorgel F.: Mesalazine pharmacokinetics and NAT2 phenotype. Eur J Clin Pharmacol. 2009; 65, 47-54. Go to original source... Go to PubMed...
    112. Grant D. M., Tang B. K., Kalow W.: A simple test for acetylator phenotype using caffeine. Br J Clin Pharmacol. 1984; 17, 459-464. Go to original source... Go to PubMed...
    113. Zusterzeel P. L., te Morsche R. H., Raijmakers M. T., Roes E. M., Peters W. H., Steegers-Theunissen R. P., Steegers E. A.: N-acetyl-transferase phenotype and risk for preeclampsia. Am J Obstet Gynecol. 2005; 193, 797-802. Go to original source... Go to PubMed...
    114. Bolt H. M., Selinski S., Dannappel D., Blaszkewicz M., Golka K.: Re-investigation of the concordance of human NAT2 phenotypes and genotypes. Arch Toxicol. 2005; 79, 196-200. Go to original source... Go to PubMed...
    115. Kennedy M. J., Abdel-Rahman S. M., Kashuba A. D., Leeder J. S.: Comparison of various urine collection intervals for caffeine and dextromethorphan phenotyping in children. J Clin Pharmacol. 2004; 44, 708-714. Go to original source... Go to PubMed...
    116. Cribb A. E., Isbrucker R., Levatte T., Tsui B., Gillespie C. T., Renton K. W.: Acetylator phenotyping: the urinary caffeine metabolite ratio in slow acetylators correlates with a marker of systemic NAT1 activity. Pharmacogenetics. 1994; 4, 166-170. Go to original source...
    117. Ellard G. A., Gammon P. T., Titinen H.: Determination of the acetylator phenotype using matrix isoniazid. Tubercle. 1975; 56, 203-209. Go to original source... Go to PubMed...
    118. Pink J. C., Messing E. M., Reznikoff C. A., Bryan G. T., Swaminathan S.: Correlation between N-acetyltransferase activities in uroepithelia and in vivo acetylator phenotype. Drug Metab Dispos. 1992; 20, 559-565. Go to original source...
    119. Stewart N. A., Buch S. C., Conrads T. P., Branch R. A.: A UPLC-MS/MS assay of the "Pittsburgh cocktail": six CYP probe-drug/metabolites from human plasma and urine using stable isotope dilution. Analyst. 2011; 136, 605-612. Go to original source... Go to PubMed...
    120. Bendriss E. K., Markoglou N., Wainer I. W.: Liquid chromatographic method for the simultaneous determination of caffeine and fourteen caffeine metabolites in urine. Journal of Chromatography B. 2000; 746, 331-338. Go to original source... Go to PubMed...
    121. Rasmussen B. B., Brosen K.: Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. Therapeutic Drug Monitoring. 1996; 18, 254-262. Go to original source... Go to PubMed...
    122. Sinues B., Saenz M. A., Lanuza J., Bernal M. L., Fanlo A., Juste J. L., Mayayo E.: Five caffeine metabolite ratios to measure tobacco-induced CYP1A2 activity and their relationships with urinary mutagenicity and urine flow. Cancer Epidemiology Biomarkers & Prevention. 1999; 8, 159-166.
    123. Kilbane A. J., Silbart L. K., Manis M., Beitins I. Z., Weber W. W.: Human N-acetylation genotype determination with urinary caffeine metabolites. Clinical Pharmacology & Therapeutics. 1990; 47, 470-477. Go to original source... Go to PubMed...
    124. Krul C., Hageman G.: Analysis of urinary caffeine metabolites to assess biotransformation enzyme activities by reversed-phase high-performance liquid chromatography. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 1998; 709, 27-34. Go to original source... Go to PubMed...
    125. Klassen R., Stavric B.: HPLC separation of theophylline, paraxanthine, theobromine, caffeine and other caffeine metabolites in biological-fluids. Journal of Liquid Chromatography. 1983; 6, 895-906. Go to original source...
    126. Miceli J. N., Chapman W.: Measurement of Caffeine Metabolites in Urine Using Diode-Array Detection Hplc. Journal of Liquid Chromatography. 1990; 13, 2239-2251. Go to original source...
    127. Nyeki A., Biollaz J., Kesselring U. W., Decosterd L. A.: Extractionless method for the simultaneous high-performance liquid chromatographic determination of urinary caffeine metabolites for N-acetyltransferase 2, cytochrome P450 1A2 and xanthine oxidase activity assessment. Journal of Chromatography B. 2001; 755, 73-84. Go to original source... Go to PubMed...
    128. Schneider H., Ma L., Glatt H.: Extractionless method for the determination of urinary caffeine metabolites using high-performance liquid chromatography coupled with tandem mass spectrometry. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 2003; 789, 227-237. Go to original source... Go to PubMed...
    129. Weimann A., Sabroe M., Poulsen H. E.: Measurement of caffeine and five of the major metabolites in urine by high-performance liquid chromatography/tandem mass spectrometry. Journal of Mass Spectrometry. 2005; 40, 307-316. Go to original source... Go to PubMed...
    130. Fang L., Pan Y., Muzyka J. L., Zhan C. G.: Active site gating and substrate specificity of butyrylcholinesterase and acetylcholinesterase: insights from molecular dynamics simulations. J Phys Chem B. 2011; 115, 8797-8805. Go to original source... Go to PubMed...
    131. Dubbels R., Schloot W.: Studies on the metabolism of benoxinate by human pseudocholinesterase. Metab Pediatr Syst Ophthalmol. 1983; 7, 37-43.
    132. Tunek A., Levin E., Svensson L. A.: Hydrolysis of 3H-bambuterol, a carbamate prodrug of terbutaline, in blood from humans and laboratory animals in vitro. Biochem Pharmacol. 1988; 37, 3867-3876. Go to original source... Go to PubMed...
    133. Gorelick D. A.: Enhancing cocaine metabolism with butyrylcholinesterase as a treatment strategy. Drug Alcohol Depend. 1997; 48, 159-165. Go to original source... Go to PubMed...
    134. Kalow W., Genest K.: A method for the detection of atypical forms of human serum cholinesterase; determination of dibucaine numbers. Can J Biochem Physiol. 1957; 35, 339-346. Go to original source...
    135. Harris H., Whittaker M.: Differential inhibition of human serum cholinesterase with fluoride: recognition of two new phenotypes. Nature. 1961; 191, 496-498. Go to original source... Go to PubMed...
    136. Goodall R.: Cholinesterase: phenotyping and genotyping. Ann Clin Biochem. 2004; 41, 98-110. Go to original source... Go to PubMed...
    137. King J., Griffin D.: Differentiation of serum cholinesterase variants by succinyldicholine inhibition. Br J Anaesth. 1973; 45, 450-454. Go to original source... Go to PubMed...
    138. Whittaker M.: The pseudocholinesterase variants. Differentiation by means of sodium chloride. Acta Genet Stat Med. 1968; 18, 556-562. Go to original source... Go to PubMed...
    139. Picheth G., Fadel-Picheth C., Primo-Parmo S. L., Chautard-Freire-Maia E. A., Vieira M. M.: An improved method for butyrylcholinesterase phenotyping. Biochem Genet. 1994; 32, 83-89. Go to original source... Go to PubMed...
    140. Whittaker M.: Differential Inhibition of Human Serum Cholinesterase with n-butyl alcohol: recognition of new phenotypes. Human Heredity. 1968; 18, 335-340. Go to original source...
    141. Garry P. J., Routh J. I.: A Micro Method for Serum Cholinesterase. Clin Chem. 1965; 11, 91-96. Go to original source...
    142. Silk E., King J., Whittaker M.: Scientific Review No. 5. Assay of cholinesterase in clinical chemistry. Ann Clin Biochem. 1979; 16, 57-75. Go to original source... Go to PubMed...
    143. Dietz A. A., Rubinstein H. M., Lubrano T.: Colorimetric determination of serum cholinesterase and its genetic variants by the propionylthiocholine-dithiobis(nitrobenzoic acid.procedure. Clin Chem. 1973; 19, 1309-1313. Go to original source...
    144. Slanar O., Chalupna P., Novotny A., Bortlik M., Krska Z., Lukas M.: Fatal myelotoxicity after azathioprine treatment. Nucleosides Nucleotides Nucleic Acids. 2008; 27, 661-665. Go to original source... Go to PubMed...
    145. Slanar O., Bortlik M., Buzkova H., Donoval R., Pechandova K., Sebesta I., Lukas M., Perlik F.: Polymorphisms of the TPMT gene in the Czech healthy population and patients with inflammatory bowel disease. Nucleosides Nucleotides Nucleic Acids. 2008; 27, 835-838. Go to original source... Go to PubMed...
    146. Anglicheau D., Sanquer S., Loriot M. A., Beaune P., Thervet E.: Thiopurine methyltransferase activity: new conditions for reversed-phase high-performance liquid chromatographic assay without extraction and genotypic-phenotypic correlation. J Chromatogr B Analyt Technol Biomed Life Sci. 2002; 773, 119-127. Go to original source... Go to PubMed...
    147. Ridge S. A., Sludden J., Brown O., Robertson L., Wei X., Sapone A., Fernandez-Salguero P. M., Gonzalez F. J., Vreken P., van Kuilenburg A. B., van Gennip A. H., McLeod H. L.: Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjects. Br J Clin Pharmacol. 1998; 46, 151-156. Go to original source... Go to PubMed...
    148. Ridge S. A., Sludden J., Wei X., Sapone A., Brown O., Hardy S., Canney P., Fernandez-Salguero P., Gonzalez F. J., Cassidy J., McLeod H. L.: Dihydropyrimidine dehydrogenase pharmacogenetics in patients with colorectal cancer. Br J Cancer. 1998; 77, 497-500. Go to original source... Go to PubMed...
    149. van Kuilenburg A. B., Van Lenthe H., Tromp A., Veltman P. C., Van Gennip A. H.: Pitfalls in the diagnosis of patients with a partial dihydropyrimidine dehydrogenase deficiency. Clin Chem. 2000; 46, 9-17. Go to original source...
    150. Ito S., Kawamura T., Inada M., Inoue Y., Hirao Y., Koga T., Kunizaki J., Shimizu T., Sato, H.: Physiologically based pharmacokinetic modelling of the three-step metabolism of pyrimidine using C-uracil as an in vivo probe. Br J Clin Pharmacol. 2005; 60, 584-593. Go to original source... Go to PubMed...
    151. Mattison L. K., Fourie J., Hirao Y., Koga T., Desmond R. A., King J. R., Shimizu T., Diasio R. B.: The uracil breath test in the assessment of dihydropyrimidine dehydrogenase activity: pharmacokinetic relationship between expired 13CO2 and plasma [2-13C]dihydrouracil. Clin Cancer Res. 2006; 12, 549-555. Go to original source... Go to PubMed...
    152. Bock K. W., Wiltfang J., Blume R., Ullrich D., Bircher J.: Paracetamol as a test drug to determine glucuronide formation in man. Effects of inducers and of smoking. Eur J Clin Pharmacol. 1987; 31, 677-683. Go to original source... Go to PubMed...
    153. Burger D. M., Huisman A., Van Ewijk N., Neisingh H., Van Uden P., Rongen G. A., Koopmans P., Bertz R. J.: The effect of atazanavir and atazanavir/ritonavir on UDP-glucuronosyltransferase using lamotrigine as a phenotypic probe. Clin Pharmacol Ther. 2008; 84, 698-703. Go to original source... Go to PubMed...
    154. Jensen L. S., Valentine J., Milne R. W., Evans A. M.: The quantification of paracetamol, paracetamol glucuronide and paracetamol sulphate in plasma and urine using a single high-performance liquid chromatography assay. Journal of Pharmaceutical and Biomedical Analysis. 2004; 34, 585-593. Go to original source... Go to PubMed...
    155. Di Girolamo A., O'Neill W. M., Wainer I. W.: A validated method for the determination of paracetamol and its glucuronide and sulphate metabolites in the urine of HIV+/AIDS patients using wavelength-switching UV detection. Journal of Pharmaceutical and Biomedical Analysis. 1998; 17, 1191-1197. Go to original source... Go to PubMed...
    156. Oliveira E. J., Watson D. G., Morton N. S.: A simple microanalytical technique for the determination of paracetamol and its main metabolites in blood spots. Journal of Pharmaceutical and Biomedical Analysis. 2002; 29, 803-809. Go to original source... Go to PubMed...
    157. Alobaidy S. S., Po A. L. W., Mckiernan P. J., Glasgow J. F. T., Millership J.: Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver-disease. Journal of Pharmaceutical and Biomedical Analysis. 1995; 13, 1033-1039. Go to original source... Go to PubMed...
    158. Goicoechea A. G., Dealda M. J. L., Vilajato J. L.: A validated high-performance liquid-chromatographic method for the determination of paracetamol and its major metabolites in urine. Journal of Liquid Chromatography. 1995; 18, 3257-3268. Go to original source...
    159. Adriaenssens P. I., Prescott L. F.: High-performance liquid-chromatographic estimation of paracetamol metabolites in plasma. British Journal of Clinical Pharmacology. 1978; 6, 87-88. Go to original source... Go to PubMed...
    160. Baranowska I., Wilczek A.: Simultaneous RP-HPLC determination of sotalol, metoprolol, alpha-hydroxymetoprolol, paracetamol and its glucuronide and sulfate metabolites in human urine. Analytical Sciences. 2009; 25, 769-772. Go to original source... Go to PubMed...
    161. Lau G. S., Critchley J. A.: The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatography assay. J Pharm Biomed Anal. 1994; 12, 1563-1572. Go to original source... Go to PubMed...
    162. Videau O., Delaforge M., Levi M., Thevenot E., Gal O., Becquemont L., Beaune P., Benech H.: Biochemical and analytical development of the CIME cocktail for drug fate assessment in humans. Rapid Commun Mass Spectrom. 2010; 24, 2407-2419. Go to original source... Go to PubMed...
    163. Christensen M., Andersson K., Dalen P., Mirghani R. A., Muirhead G. J., Nordmark A., Tybring G., Wahlberg A., Yasar U., Bertilsson L.: The Karolinska cocktail for phenotyping of five human cytochrome P450 enzymes. Clin Pharmacol Ther. 2003; 73, 517-528. Go to original source... Go to PubMed...
    164. Streetman D. S., Bleakley J. F., Kim J. S., Nafziger A. N., Leeder J. S., Gaedigk A., Gotschall R., Kearns G. L., Bertino J. S. Jr.: Combined phenotypic assessment of CYP1A2, CYP2C19, CYP2D6, CYP3A, N-acetyltransferase-2, and xanthine oxidase with the "Cooperstown cocktail". Clin Pharmacol Ther. 2000; 68, 375-383. Go to original source... Go to PubMed...
    165. Chainuvati S., Nafziger A. N., Leeder J. S., Gaedigk A., Kearns G. L., Sellers E., Zhang Y., Kashuba A. D., Rowland E., Bertino J. S. Jr.: Combined phenotypic assessment of cytochrome p450 1A2, 2C9, 2C19, 2D6, and 3A, N-acetyltransferase-2, and xanthine oxidase activities with the "Cooperstown 5+1 cocktail". Clin Pharmacol Ther. 2003; 74, 437-447. Go to original source... Go to PubMed...
    166. Zhu B., Ou-Yang D. S., Chen X. P., Huang S. L., Tan Z. R., He N., Zhou, H. H.: Assessment of cytochrome P450 activity by a five-drug cocktail approach. Clin Pharmacol Ther. 2001; 70, 455-461. Go to original source...

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