Pharmacogenetic diagnostics of cytochrome P450 polymorphisms in clinical drug development and in drug treatment

Pharmacogenomics

Volumn 1, Issue 2, 2000, Pages 125-151

  Brockmöller, Jürgen ^a,b   Kirchheiner, Julia ^a   Meisel, Christian ^a   Roots, Ivar ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^b HUMBOLDT UNIVERSITY   (Germany)

Author keywords

Assay validation; CYP2A6; CYP2C19; CYP2C9; CYP2D6; Cytochrome P450; Dose adjustment; Drug development; Genotyping; Pharmacogenetics; Polymerase chain reaction (PCR); Polymorphism

Indexed keywords

CYTOCHROME P450;

ANIMAL; CLINICAL PHARMACOLOGY; DRUG THERAPY; GENETIC POLYMORPHISM; GENETICS; HUMAN; REVIEW;

ANIMALS; CYTOCHROME P-450 ENZYME SYSTEM; DRUG THERAPY; HUMANS; PHARMACOLOGY, CLINICAL; POLYMORPHISM, GENETIC;

EID: 0034188949     PISSN: 14622416     EISSN: None     Source Type: Journal    
DOI: 10.1517/14622416.1.2.125     Document Type: Review

References (127)

1. ANDERSSON T: Omeprazole drug interaction studies. Clin. Pharmacokinet. (1991) 21(3):195-212. One of the first reviews using CYP enzyme specificity to classify drug interactions.
2. BROCKMÖLLER J, ROOTS I: Assessment of liver metabolic function. Clinical implications. Clin. Pharmacokinet. (1994) 27(3):216-248. Additional reference for CYP phenotyping procedures.
3. NELSON DR, KOYMANS L, KAMATAKI T et al.: P450 superfamily: update of new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics (1996) 6:1-42. CYP nomenclature and classification.
4. GONZALEZ FJ, NEBERT DW: Evolution of the P450 gene superfamily: animal plant 'warfare', molecular drive and human genetic differences in drug oxidation. Trends Genet. (1990) 6:182-186. Evolutionary concepts in CYP diversity.
5. BERTZ RJ, GRANNEMAN GR: Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin. Pharmacokinet. (1997) 32(3):210-258. Valuable data source for CYP-specific drug metabolism.
6. EICHELBAUM M: Ein neuentdeckter Defekt im Arzneimittel-Stoffwechsel des Menschen: die fehlende N-Oxidation des Spartein. Habilitationsschrift. Medizinische Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn. (1975). Pioneering work on CYP2D6 polymorphism.
7. MAHGOUB A, IDLE JR, DRING LG, LANCASTER R, SMITH RL: Polymorphic hydroxylation of debrisoquine in man. Lancet (1977) 2(8038):584-586. The second pioneering work on CYP2D6 polymorphism.
8. KIMURA S, UMENO M, SKODA RC, MEYER UA, GONZALEZ FJ: The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene and a pseudogene. Am. J. Hum. Genet. (1989) 45(6):889-904. Basic DNA sequence data source for all those analysing CYP2D6 polymorphisms.
9. GONZALEZ FJ, SKODA RC, KIMURA S et al.: Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature (1988) 331(6155):442-446. Pioneering work to isolate the CYP2D6 gene
10. HEIM M, MEYER UA: Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification. Lancet (1990) 336(8714):529-532. First really successful CYP2D6 genotyping.
11. DALY AK, BROCKMÖLLER J, BROLY F et al: Nomenclature for human CYP2D6 alleles. Pharmacogenetics (1996) 6(3):193-201. Compilation and nomenclature for major CYP2D6 variants, now available via internet [203].
12. SACHSE C, BROCKMÖLLER J, BAUER S, ROOTS I: Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am. J. Hum. Genet. (1997) 60(2):284-295. One answer to the question: how many variants have to be tested for sufficiently accurate prediction of CYP2D6 phenotype by genotyping?
13. KUTT H, WOLK M, MC DOWELL F: Insufficient parahydroxylation as a cause of diphenylhydantoin toxicity. Neurology (1964) 14:542-548. Probably the first work indicating probable genetic phenytoin metabolic polymorphism, now known to be due to CYP2C9 genetic variants.
14. SCOTT J, POFFENBARGER PL: Pharmacogenetics of tolbutamide metabolism in humans. Diabetes (1979) 28(1):41-51-Probably the first work indicating polymorphic tolbutamide metabolism, now known to be due to CYP2C9 gene variants.
15. KÜPFER A, PREISIG R: Pharmacogenetics of mephenyloin: a new drug hydroxylation polymorphism in man. Eur. J. Clin. Pharmacol. (1984) 26(6):753-759. Probably the first work to show the genetic polymorphism in mephenytoin hydroxylation, now known to be determined by CYP2C19 polymorphism.
16. DE MORAIS SMF, WILKINSON GR, BLAISDELL J et al.: Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol. Pharmacol, (1994) 46(4):594-598. Pioneering work to identify the molecular basis of the CYP2C19 polymorphism.
17. CASCORBI I, BROCKMÖLLER J, ROOTS I: A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages and impact on lung cancer susceptibility. Cancer Res. (1996) 56:4965-4969. On CYP1A1 gene variants and their genetic linkage.
18. PERSSON I, JOHANSSON I, INGELMAN-SUNDBERG M: In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility. Biochem. Biophys. Res. Commun. (1997) 231:227-230. Work on the controversial functional effects of CYP1A1 polymorphisms.
19. FERNANDEZ-SALGUERO P, HOFFMAN SM, CHOLERTON S et al.: A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. Am. J. Hum. Genet. (1995) 57:651-660. Pioneering work to sequence the CYP2A gene cluster and identify its first gene polymorphism.
20. OSCARSON M, GULLSTÉN H, RAUTIO A et al.: Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. FEBS Lett. (1998) 438:201-205. Important update on CYP2A6 genetic polymorphisms.
21. OSCARSON M, MCLELLAN RA, GULLSTÉN H et al.: Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett. (1999) 460:321-327. Another update on CYP2A5 genetic polymorphisms.
22. NAKAJIMA M, YAMAGISHI S-I, YAMAMOTO H, YAMAMOTO T, KUROIWA Y, YOKOI T: Deficient cotinine formation from nicotine is attributed to the whole deletion of the CYP2A6 gene in humans. Clin. Pharmacol. Ther. (2000) 67:57-70. One illustration of the importance of CYP2A6 for nicotine metabolism.
23. MINERS JO, BIRKETT DJ: Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br. J. Clin. Pharmacol. (1998) 45:525-538. Comprehensive review on CYP2C9.
24. HIROI T, IMAOKA S, FUNAE Y: Dopamine formation from tyramine by CYP2D6. Biochem. Biophys. Res. Comm. (1998) 249:838-843. Interesting with respect to our understanding of the role of CYP2D6 in endogenous metabolism and possibly CNS disease.
25. HU Y, OSCARSON M, JOHANSSON I et al.: Genetic polymorphism of human CYP2E1: characterization of two variant alleles. Mol. Pharmacol. (1997) 51:370-376. Rare but functional CYP2E1 variants.
26. HAYASHI S, WATANABE J, KAWAJIRI K: Genetic polymorphisms in the 5′-flanking regions change transcriptional regulation of the human cytochrome P450 IIE1 gene. J. Biochem. (Tokyo) (1991) 110:559-565. Frequent, and subsequently frequently studied, CYP2E1 variants with still equivocal functional relevance.
27. CARRIERE V, BERTHOU F, BAIRD S, BELLOC C, BEAUNE P, DE WAZIERS I: Human cytochrome P450 2E1 (CYP2E1): from genotype to phenotype. Pharmacogenetics (1996) 6:203-211. Further clarification of the functional relevance of the frequent CYP2E1 variants.
28. WESTLIND A, LOFBERG L, TINDBERG N, ANDERSSON TB, INGELMAN SUNDBERG M: Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5′-upstream regulatory region. Biochem. Biophys. Res. Commun. (1999) 259(1):201-205. CYP3A4 genetic variants: an upcoming and important area of research.
29. SATA F, SAPONE A, ELIZONDO G et al.: CYP3A4 allelic variants with amino acid substitutions in exon 7 and 12: evidence for an allelic variant with altered catalytic activity. Clin. Pharm. Ther. (2000) 67:48-57. Two functional, though relatively rare, CYP3A4 variants.
30. GORSKI JC, JONES DR, HAMMAN MA, WRIGHTON SA, HALL SD: Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily. Xenobiotica (1999) 29:931-944. Alprazolam as a new CYP3A4 probe: biochemical data.
31. SCHMIDER J, BROCKMÖLLER J, AROLD G, BAUER S, ROOTS I: Simultaneous assessment of CYP3A4 and CYP1A2 activity in vivo with alprazolam and caffeine. Pharmacogenetics (1999) 9:725-734. Alprazolam as a new CYP3A4 probe not having the disadvantage of being a high clearance drug: clinical validation.
32. KENWORTHY KE, BLOOMER JC, CLARKE SE, HOUSTON JB: CYP3A4 drug interactions: correlation of 10 in vitro probe substrates. Br. J. Clin. Pharmacol. (1999) 48:716-727. Important data for anyone who is interested in CYP3A4 phenotyping.
33. HOFFMEYER S, BURK O, VON RICHTER O et al.: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad. Sci. USA (2000) 97:3473-3478. Recent data on extensive genetic polymorphism in drug transport.
34. GOODWIN B, HODGSON E, LIDDLE C: The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol. Pharmacol. (1999) 56:1329-1339. Data to understand polymorphic activity of CYP3A4.
35. WAXMAN DJ: P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR and PPAR. Arch. Biochem. Biophys. (1999) 369(1):11-23. Data to understand polymorphic activity of CYP3A4.
36. BROCKMÖLLER J, BRÄUTIGAM K, MAI I, BAUER S, ROST K, ROOTS I: Combined CYP3A4 inhibition and CYP2C19 deficiency: consequences for disposition of omeprazole and its enantiomers. Clin. Pharmacol. Ther. (1997) 61(2):171. First publication of the omeprazole data illustrated in Figure 3 and used to demonstrate value of CYP genotyping in drug trials.
37. JOHANSSON I, LUNDQVIST E, BERTILSSON L, DAHL ML, SJÖQVIST F, INGELMAN SUNDBERG M: Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc. Natl. Acad. Sci. USA (1993) 90(24):11825-11829. Genetic characterisation of one basis of ultra-rapid metabolism.
38. MELLSTRÖM B, BERTILSSON L, LOU YC, SÄWE J, SJÖQVIST F: Amitriptyline metabolism: relationship to polymorphic debrisoquine hydroxylation. Clin. Pharmacol. Ther. (1983) 34(4):516-520.
39. FROMM MF, HOFMANN U, GRIESE EU, MIKUS G: Dihydrocodeine: a new opioid substrate for the polymorphic CYP2D6 in humans. Clin. Pharmacol. Ther. (1995) 58(4):374-382.
40. SUZUKI A, OTANI K, MIHARA K et al: Effects of the CYP2D6 genotype on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese schizophrenic patients. Pharmacogenetics (1997) 7(5):415-418.
41. MIHARA K, SUZUKI A, KONDO T et al.: Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia. Clin. Pharmacol. Ther. (1999) 65(3):291-294.
42. BERTILSSON L, EICHELBAUM M, MELLSTRÖM B, SÄWE J, SCHULZ HU, SJÖQVIST F: Nortriptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man. Life Sci. (1980) 27(18):1673-1677.
43. DALÉN P, DAHL ML, RUIZ ML, NORDIN J, BERTILSSON L: 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3 and 13 functional CYP2D6 genes. Clin. Pharmacol. Ther. (1998) 63(4):444-452. Illustration of the phenomenon known as gene-dose effect for CYP2D6.
44. MELLSTRÖM B, BERTILSSON L, SÄWE J, SCHULZ HU, SJÖQVIST F: E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin. Pharmacol. Ther. (1981) 30(2):189-193.
45. AYNACIOGLU A, BROCKMÖLLER J, BAUER S et al.: Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br. J. Clin. Pharmacol. (1999) 48:409-415.
46. ODANI A, HASHIMOTO Y, OTSUKI Y et al.: Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin. Pharmacol. Ther. (1997) 62(3):287-292.
47. 359 variant and their mixture versus unbound clearance in patients with the corresponding CYP2C9 genotypes. Pharmacogenetics (1998) 8(5):365-373.
48. BRØSEN K, OTTON SV, GRAM LF: Imipramine demethylation and hydroxylation: impact of the sparteine oxidation phenotype. Clin. Pharmacol. Ther. (1986) 40(5):543-549.
49. SKJELBO E, BRØSEN K, HALLAS J, GRAM LF: The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clin. Pharmacol. Ther. (1991) 49(1):18-23.
50. CHANG M, DAHL ML, TYBRING G, GOTHARSON E, BERTILSSON L: Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: comparison with 5-mephenytoin hydroxylation phenotype and CYP2C19 genotype. Pharmacogenetics (1995) 5(6):358-363.
51. SAGAR M, SEENSALU R, TYBRING G, DAHL ML, BERTILSSON L: CYP2C19 genotype and phenotype determined with omeprazole in patients with acid-related disorders with and without Helicobacter pylori infection. Scand. J. Gastroenterol. (1998) 33(10):1034-1038.
52. EAP CB, LIMA CA, MACCIARDI F, WOGGON B, POWELL K, BAUMANN P: Steady state concentrations of the enantiomers of mianserin and desmethylmianserin in poor and in homozygous and heterozygous extensive metabolizers of debrisoquine. Ther. Drug Monit. (1998) 20(1):7-13.
53. HUANG ML, VAN PEER A, WOESTENBORGHS R et al: Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin. Pharmacol. Ther. (1993) 54(3):257-268.
54. STEARNS RA, CHAKRAVARTY PK, CHEN R, CHIU SH: Biotransformation of Iosartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug Metab. Dispos. (1995) 23(2):207-215.
55. KROEMER HK, TURGEON J, PARKER RA, RODEN DM: Flecainide enantiomers: disposition in human subjects and electrophysiologic actions in vitro. Clin. Pharmacol. Ther. (1989) 46(5):584-590.
56. MIKUS G, GROSS AS, BECKMANN J, HERTRAMPF R, GUNDERT REMY U, EICHELBAUM M: The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide. Clin. Pharmacol. Ther. (1989) 45(5):562-567.
57. FUNCK BRENTANO C, BECQUEMONT L, KROEMER HK et al.: Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance and interaction with amiodarone. Clin. Pharmacol. Ther. (1994) 55(3):256-269.
58. BIRGERSDOTTER UM, WONG W, TURGEON J, RODEN DM: Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias. Br. J. Clin. Pharmacol. (1992) 33(3):275-280.
59. GROSS AS, MIKUS G, FISCHER C, HERTRAMPF R, GUNDERT REMY U, EICHELBAUM M: Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype. Br. J. Clin. Pharmacol. (1989) 28(5):555-566.
60. KROEMER HK, FUNCK BRENTANO C, SILBERSTEIN DJ et al.: Stereoselective disposition and pharmacologic activity of propafenone enantiomers. Circulation (1989) 79(5):1068-1076.
61. SIDDOWAY LA, THOMPSON KA, MCALLISTER CB et al.: Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation (1987) 75(4):785-791.
62. LATINI R, BELLONI M, BERNASCONI R et al: Identification of propafenone metaboliser phenotype from plasma and urine excretion data. Eur. J. Clin. Pharmacol. (1992) 42(1):111-114.
63. LEE JT, KROEMER HK, SILBERSTEIN DJ et al.: The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N. Engl. J. Med. (1990) 322(25):1764-1768.
64. BAUMANN P, JONZIER PEREY M, KOEB L, KÜPFER A, TINGUELY D, SCHOPF J: Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. Int. Clin. Psychopharmacol. (1986) 1(2):102-112.
65. MELLSTRÖM B, SÄWE J, BERTILSSON L, SJÖQVIST F: Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. Clin. Pharmacol. Ther. (1986) 39(4):369-371.
66. NELSON JC, MAZURE C, JATLOW PI: Antidepressant activity of 2-hydroxydesipramine. Clin. Pharmacol. Ther. (1988) 44(3):283-288.
67. BALANT GORGIA AE, SCHULZ P, DAYER P et al.: Role of oxidation polymorphism on blood and urine concentrations of amitriptyline and its metabolites in man. Arch. Psychiatr. Nervenkr. (1982) 232(3):215-222.
68. SINDRUP SH, BRØSEN K, HANSEN MG, AAES JORGENSEN T, OVERO KF, GRAM LF: Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther. Drug Monit. (1993) 15(1):11-17.
69. ROCHAT B, AMEY M, GILLET M, MEYER UA, BAUMANN P: Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics (1997) 7(1):1-10.
70. NIELSEN KK, BRØSEN K, HANSEN MG, GRAM LF: Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Clin. Pharmacol. Ther. (1994) 55(5):518-527.
71. NIELSEN KK, BRØSEN K, GRAM LF: Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group. Eur. J. Clin. Pharmacol. (1992) 43(4):405-411.
72. DUAG: Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Clin. Pharmacol. Ther. (1999) 66:152-165.
73. GRAM LF, GUENTERT TW, GRANGE S, VISTISEN K, BRØSEN K: Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2: a panel study. Clin. Pharmacol. Ther. (1995) 57(6):670-677.
74. FIRKUSNY L, KROEMER HK, EICHELBAUM M: In vitro characterization of cytochrome P450 catalysed metabolism of the antiemetic tropisetron. Biochem. Pharmacol. (1995) 49(12):1777-1784.
75. KUTZ K: Pharmacology, toxicology and human pharmacokinetics of tropisetron. Ann. Oncol. (1993) 4(Suppl. 3):15-18.
76. VERONESE ME, MACKENZIE PI, DOECKE CJ, MCMANUS ME, MINERS JO, BIRKETT DJ: Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9 [published erratum appears in Biochem. Biophys. Res. Commun. (14 Nov 1991) 18(3):1527]. Biochem. Biophys. Res. Commun. (1991) 175(3):1112-1118.
77. FRITZ S, LINDNER W, ROOTS I, FREY BM, KÜPFER A: Stereochemistry of aromatic phenytoin hydroxylation in various drug hydroxylation phenotypes in humans. J. Pharmacol. Exp. Ther. (1987) 241(2):615-622.
78. SHEINER LB, GRASELA TH: Experience with NONMEM: analysis of routine phenytoin clinical pharmacokinetic data. Drug Metab. Rev. (1984) 15(1-2):293-303. Population pharmacokinetic analysis - nowadays continued as molecular population pharmacokinetic analysis, as illustrated in the subsequent paper of Mamiya et al. [79].
79. MAMIYA K, IEIRI I, SHIMAMOTO J et al.: The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia (1998) 39(12):1317-1323. CYP2C9 polymorphism: impact for therapy with phenytoin and population kinetic analysis.
80. CHANG WH: Reduced haloperidol: a factor in determining the therapeutic benefit of haloperidol treatment? Psychopharmacology (Berlin) (1992) 106(3):289-296.
81. SOMEYA T, SUZUKI Y, SHIMODA K et al.: The effect of cytochrome P4502D6 genotypes on haloperidol metabolism: a preliminary study in a psychiatric population. Psych. Clin. Neurosci. (1999) 53:593-597.
82. GRAM LF, DEBRUYNE D, CAILLARD V et al.: Substantial rise in sparteine metabolic ratio during haloperidol treatment. Br. J. Clin. Pharmacol. (1989) 27(2):272-275.
83. LLERENA A, DAHL ML, EKQVIST B, BERTILSSON L: Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers. Ther. Drug Monit. (1992) 14(3):261-264.
84. PAN L, DE VRIENDT C, BELPAIRE F: In-vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol. Pharmacogenetics (1998) 8:383-389.
85. ARTHUR H, DAHL ML, SIWERS B, SJÖQVIST F: Polymorphic drug metabolism in schizophrenic patients with tardive dyskinesia. J. Clin. Psychopharmacol. (1995) 15(3):211-216.
86. IWAHASHI K, NAKAMURA K, SUWAKI H, TSUNEOKA Y, ICHIKAWA Y: CYP2D6 Hhal genotype and the neuroleptic malignant syndrome (NMS). Clin. Chim. Acta. (1997) 265(1):143-144.
87. SPINA E, ANCIONE M, DI ROSA AE, MEDURI M, CAPUTI AP: Polymorphic debrisoquine oxidation and acute neuroleptic-induced adverse effects. Eur. J. Clin. Pharmacol. (1992) 42(3):347-348.
88. DAHL ML, EKQVIST B, WIDEN J, BERTILSSON L: Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans. Acta. Psychiatr. Scand. (1991) 84(1):99-102.
89. JERLING M, DAHL ML, ABERG WISTEDT A et al.: The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clin. Pharmacol. Ther. (1996) 59(4):423-428.
90. LINNET K, WIBORG O: Influence of Cyp2D6 genetic polymorphism on ratios of steady-state serum concentration to dose of the neuroleptic zuclopenthixol. Ther. Drug Monit. (1996) 18(6):629-634.
91. BERTILSSON L, HENTHORN TK, SANZ E, TYBRING G, SÄWE J, VILLEN T: Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin. Pharmacol. Ther. (1989) 45(4):348-355.
92. ISHIZAKI T, CHIBA K, MANABE K et al.: Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4′-hydroxylation. Clin. Pharmacol. Ther. (1995) 58(2):155-164.
93. SOHN DR, KUSAKA M, ISHIZAKI T et al.: Incidence of S-mephenytoin hydroxylation deficiency in a Korean population and the interphenotypic differences in diazepam pharmacokinetics. Clin. Pharmacol. Ther. (1992) 52(2):160-169.
94. ZHOU HH, WOOD AJ: Stereoselective disposition of carvedilol is determined by CYP2D6. Clin. Pharmacol. Ther. (1995) 57(5):518-524.
95. LENNARD MS, SILAS JH, FREESTONE S, RAMSAY LE, TUCKER GT, WOODS HF: Oxidation phenotype - a major determinant of metoprolol metabolism and response. N. Engl. J. Med. (1982) 307(25):1558-1560.
96. BORG KO, CARLSSON E, HOFFMANN KJ, JONSSON TE, THORIN H, WALLIN B: Metabolism of metoprolol-(3-h) in man, the dog and the rat. Acta. Pharmacol. Toxicol. Copenh, (1975) 36(5):125-135.
97. LENNARD MS, TUCKER GT, SILAS JH, FREESTONE S, RAMSAY LE, WOODS HF: Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. Clin. Pharmacol. Ther. (1983) 34(6):732-737.
98. KOYTCHEV R, ALKEN RG, VLAHOV V et al.: Influence of the cytochrome P4502D6*4 allele on the pharmacokinetics of controlled-rclease metoprolol. Eur. J. Clin. Pharmacol. (1998) 54(6):469-474.
99. MCGOURTY JC, SILAS JH, LENNARD MS, TUCKER GT, WOODS HF: Metoprolol metabolism and debrisoquine oxidation polymorphism - population and family studies. Br. J. Clin. Pharmacol. (1985) 20(6):555-566.
100. SILAS JH, MCGOURTY JC, LENNARD MS, TUCKER GT, WOODS HF: Polymorphic metabolism of metoprolol: clinical studies. Eur. J. Clin. Pharmacol. (1985) 28(Suppl.):85-88.
101. POULSEN L, BROSEN K, ARENDT NIELSEN L, GRAM LF, ELBAEK K, SINDRUP SH: Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect and side effects. Eur. J. Clin. Pharmacol. (1996) 51(3-4):289-295.
102. DALEN P, FRENGELL C, DAHL ML, SJÖQVIST F: Quick onset of severe abdominal pain after codeine in an ultrarapid metabolizer of debrisoquine. Ther. Drug Monit. (1997) 19(5):543-544.
103. PICHARD L, CURI PEDROSA R, BONFILS C et al: Oxidative metabolism of lansoprazole by human liver cytochromes P450. Mol. Pharmacol. (1995) 47(2):410-418.
104. ANDERSSON T: Pharmacokinetics, metabolism and interactions of acid pump inhibitors. Focus on omeprazole, lansoprazole and pantoprazole [published erratum appears in Clin. Pharmacokinet. (Oct 1996) 31(4):274]. Clin. Pharmacokinet. (1996) 31(1):9-28.
105. ERLANDSSON P, ISAKSSON R, LORENTZON P, LINDBERG P: Resolution of the enantiomers of omeprazole and some of its analogues by liquid chromatography on a trisphenylcarbamoylcellulose-based stationary phase. The effect of the enantiomers of omeprazole on gastric glands. J. Chromatogr. (1990) 532(2):305-319.
106. ANDERSSON T, REGARDH CG, DAHL PUUSTINEN ML, BERTILSSON L: Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. Ther. Drug Monit. (1990) 12(4):415-416.
107. ROST KL, ROOTS I: Nonlinear kinetics after high-dose omeprazole caused by saturation of genetically variable CYP2C19. Hepatotogy(1996) 23(6):1491-1497. Demonstration of the limitations of single dose studies for pharmacogenetic analysis.
108. ANDERSSON T, MINERS JO, VERONESE ME, BIRKETT DJ: Identification of human liver cytochrome P450 isoforms mediating secondary omeprazole metabolism. Br. J. Clin. Pharmacol. (1994) 37(6):597-604.
109. CHANG M, TYBRING G, DAHL ML et al.: Interphenotype differences in disposition and effect on gastrin levels of omeprazole - suitability of omeprazole as a probe for CYP2C19. Br. J. Clin. Pharmacol. (1995) 39(5):511-518. CYP2C19 dependence of gastrin as a surrogate parameter of omeprazole effect.
110. ROST KL, BRÖSICKE H, BROCKMÖLLER J, SCHEFFLER M, HELGE H, ROOTS I: Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin. Pbarmacol. Ther. (1992) 52(2):170-180.
111. FURUTA T, OHASHI K, KOSUGE K et al.: CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin. Pharmacol. Ther. (1999) 65(5):552-561.
112. RELLING MV, AOYAMA T, GONZALEZ FJ, MEYER UA: Tolbutamide and mephenytoin hydroxylatlon by human cytochromc P450s in the CYP2C subfamily. J. Pharmacol. Exp. Ther. (1990) 252(1):442-447.
113. PEART GF, BOUTAGY J, SHENFIELD GM: Lack of relationship between tolbutamide metabolism and debrisoquine oxidation phenotype. Eur. J. Clin. Pharmacol. (1987) 33(4):397-402.
114. 359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics (1996) 6(4):341-349.
115. RIEUTORD A, STUPANS I, SHENFIELD GM, GROSS AS: Gliclazide hydroxylation by rat liver microsomes. Xenobiotica (1995) 25(12):1345-1354.
116. KIDD RS, STRAUGHN AB, MEYER MC, BLAISDELL J, GOLDSTEIN JA, DALTON JT: Pharmacokinctics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics (1999) 9(1):71-80.
117. O'REILLY RA: Studies on the optical enantiomorphs of warfarin in man. Clin. Pharmacol. Ther. (1974) 16(2):348-354.
118. RETTIE AE, KORZEKWA KR, KUNZE KL et al.: Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem. Res. Toxicol. (1992) 5(1):54-59.
119. STEWARD DJ, HAINING RL, HENNE KR et al.: Genetic association between sensitivity to warfarin and expression of CYP2C9*3. Pharmacogenetics (1997) 7(5):361-367.
120. OGG MS, BRENNAN P, MEADE T, HUMPHRIES SE: CYP2C9*3 allelic variant and bleeding complications. Lancet (1999) 354(9184):1124.
121. FURUYA H, FERNANDEZ SALGUERO P, GREGORY W et al.: Genetic polymorphism of CYP2C9 and its effect on warfarin maintenance dose requirement in patients undergoing anticoagulation therapy. Pharmacogenetics (1995) 5(6):389-392.
122. AITHAL GP, DAY CP, KESTEVEN PJ, DALY AK: Association of polymorphisms in the cytochrome P450 CYP2C9 with warfarin dose requirement and risk of bleeding complications. Lancet (1999) 353(9154):717-719. Demonstration of the medical relevance of the CYP2C9 polymorphism in warfarin treatment.
123. INGELMAN-SUNDBERG M, OSCARSON M, MCLELLAN RA: Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment. Trends Pharmacol. Sci. (1999) 20:342-349. Recent comprehensive review on CYP polymorphisms.
124. http://dmelson.utmem.edu/CytochromeP450.html UT MEMPHIS, DEPT. OF BIOCHEMISTRY: Cytochrome P450 homepage. (1993). Most recent CYP gene data.
125. http://dml.georgetown.edu/depts/pharmacology/davetab. html GEORGETOWN UNIVERSITY MEDICAL CENTER PHARMACOLOGY HOME PAGE: Cytochrome P450 drug interaction table. (1998). Data on cytochrome P450 enzyme-specific drug metabolism.
126. http://www.imm.ki.se/CYPalleles/ KAROLINSKA INSTITUTET NATIONAL INSTITUTE OF ENVIRONMENTAL MEDICINE: Human cytochrome P450 (CYP) allele nomenclature committee. (1999). Summary and nomenclature of CYP allele variants.
127. http://www.cochrane.org/ COCHRANE COLLABORATION: Preparing, maintaining and promoting the accessibility of systematic reviews of the effects of health care interventions. (1997). Systematic summary of medically relevant clinical trials. Important source for anyone who performs clinical studies.