Skip to main content
Journal of Psychiatry & Neuroscience: JPN logoLink to Journal of Psychiatry & Neuroscience: JPN
. 1994 Jan;19(1):30–44.

Polymorphism in the metabolism of drugs, including antidepressant drugs: comments on phenotyping.

R T Coutts 1
PMCID: PMC1188560  PMID: 8148364

Abstract

In neurochemistry there are advantages in determining how patients are likely to react to psychoactive drugs prior to the commencement of drug therapy. Explanations of a patient's nonresponse, or unexpected adverse reactions to drugs are required. In many instances, a knowledge of the drug metabolism status of a patient can be helpful in the selection of a drug and its dosage regimen, and in the prediction of possible drug/drug interactions when two or more drugs have to be administered concomitantly. Important information on these topics may be obtained by phenotyping patients prior to drug therapy. The metabolism of various antidepressant and neuroleptic drugs is catalyzed by CYP2D6, a cytochrome P450 isozyme (also named P450IID6), whereas the metabolism of other drugs may involve different cytochromes P450. The properties of CYP2D6 and four other isozymes (CYP1A1, CYP1A2, CYP2C8/9 and CYP3A4) are described, and substrates identified. Phenotyping of patients for CYP2D6 activity and mephenytoin hydroxylase activity is described.

Full text

PDF
30

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen J. G., Brown A. N., Marten T. R. Metabolism of debrisoquine sulphate in rat, dog and man. Xenobiotica. 1976 Jul;6(7):405–409. doi: 10.3109/00498257609151653. [DOI] [PubMed] [Google Scholar]
  2. Allen J. G., East P. B., Francis R. J., Haigh J. L. Metabolism of debrisoquine sulfate. Identification of some urinary metabolites in rat and man. Drug Metab Dispos. 1975 Sep-Oct;3(5):332–337. [PubMed] [Google Scholar]
  3. Aranow A. B., Hudson J. I., Pope H. G., Jr, Grady T. A., Laage T. A., Bell I. R., Cole J. O. Elevated antidepressant plasma levels after addition of fluoxetine. Am J Psychiatry. 1989 Jul;146(7):911–913. doi: 10.1176/ajp.146.7.911. [DOI] [PubMed] [Google Scholar]
  4. Baer A. N., McAllister C. B., Wilkinson G. R., Woosley R. L., Pincus T. Altered distribution of debrisoquine oxidation phenotypes in patients with systemic lupus erythematosus. Arthritis Rheum. 1986 Jul;29(7):843–850. doi: 10.1002/art.1780290705. [DOI] [PubMed] [Google Scholar]
  5. Balant-Gorgia A. E., Balant L. P., Genet C., Dayer P., Aeschlimann J. M., Garrone G. Importance of oxidative polymorphism and levomepromazine treatment on the steady-state blood concentrations of clomipramine and its major metabolites. Eur J Clin Pharmacol. 1986;31(4):449–455. doi: 10.1007/BF00613523. [DOI] [PubMed] [Google Scholar]
  6. Balant-Gorgia A. E., Balant L., Zysset T. High plasma concentrations of desmethylclomipramine after chronic administration of clomipramine to a poor metabolizer. Eur J Clin Pharmacol. 1987;32(1):101–102. doi: 10.1007/BF00609967. [DOI] [PubMed] [Google Scholar]
  7. Ball S. E., Maurer G., Zollinger M., Ladona M., Vickers A. E. Characterization of the cytochrome P-450 gene family responsible for the N-dealkylation of the ergot alkaloid CQA 206-291 in humans. Drug Metab Dispos. 1992 Jan-Feb;20(1):56–63. [PubMed] [Google Scholar]
  8. Barbeau A., Cloutier T., Roy M., Plasse L., Paris S., Poirier J. Ecogenetics of Parkinson's disease: 4-hydroxylation of debrisoquine. Lancet. 1985 Nov 30;2(8466):1213–1216. doi: 10.1016/s0140-6736(85)90743-3. [DOI] [PubMed] [Google Scholar]
  9. Berthou F., Flinois J. P., Ratanasavanh D., Beaune P., Riche C., Guillouzo A. Evidence for the involvement of several cytochromes P-450 in the first steps of caffeine metabolism by human liver microsomes. Drug Metab Dispos. 1991 May-Jun;19(3):561–567. [PubMed] [Google Scholar]
  10. Bock J. L., Nelson J. C., Gray S., Jatlow P. I. Desipramine hydroxylation: variability and effect of antipsychotic drugs. Clin Pharmacol Ther. 1983 Mar;33(3):322–328. doi: 10.1038/clpt.1983.40. [DOI] [PubMed] [Google Scholar]
  11. Boobis A. R., Sesardic D., Murray B. P., Edwards R. J., Singleton A. M., Rich K. J., Murray S., de la Torre R., Segura J., Pelkonen O. Species variation in the response of the cytochrome P-450-dependent monooxygenase system to inducers and inhibitors. Xenobiotica. 1990 Nov;20(11):1139–1161. doi: 10.3109/00498259009046835. [DOI] [PubMed] [Google Scholar]
  12. Brosen K. Recent developments in hepatic drug oxidation. Implications for clinical pharmacokinetics. Clin Pharmacokinet. 1990 Mar;18(3):220–239. doi: 10.2165/00003088-199018030-00004. [DOI] [PubMed] [Google Scholar]
  13. Brøsen K., Davidsen F., Gram L. F. Quinidine kinetics after a single oral dose in relation to the sparteine oxidation polymorphism in man. Br J Clin Pharmacol. 1990 Feb;29(2):248–253. doi: 10.1111/j.1365-2125.1990.tb03628.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Brøsen K., Gram L. F. Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur J Clin Pharmacol. 1989;36(6):537–547. doi: 10.1007/BF00637732. [DOI] [PubMed] [Google Scholar]
  15. Brøsen K., Gram L. F., Kragh-Sørensen P. Extremely slow metabolism of amitriptyline but normal metabolism of imipramine and desipramine in an extensive metabolizer of sparteine, debrisoquine, and mephenytoin. Ther Drug Monit. 1991 Mar;13(2):177–182. doi: 10.1097/00007691-199103000-00015. [DOI] [PubMed] [Google Scholar]
  16. Brøsen K., Gram L. F. Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine. Eur J Clin Pharmacol. 1989;37(2):155–160. doi: 10.1007/BF00558224. [DOI] [PubMed] [Google Scholar]
  17. Brøsen K., Skjelbo E. Fluoxetine and norfluoxetine are potent inhibitors of P450IID6--the source of the sparteine/debrisoquine oxidation polymorphism. Br J Clin Pharmacol. 1991 Jul;32(1):136–137. doi: 10.1111/j.1365-2125.1991.tb05630.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Brøsen K., Zeugin T., Meyer U. A. Role of P450IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine. Clin Pharmacol Ther. 1991 Jun;49(6):609–617. doi: 10.1038/clpt.1991.77. [DOI] [PubMed] [Google Scholar]
  19. Caporaso N. E., Shields P. G., Landi M. T., Shaw G. L., Tucker M. A., Hoover R., Sugimura H., Weston A., Harris C. C. The debrisoquine metabolic phenotype and DNA-based assays: implications of misclassification for the association of lung cancer and the debrisoquine metabolic phenotype. Environ Health Perspect. 1992 Nov;98:101–105. doi: 10.1289/ehp.9298101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ciraulo D. A., Shader R. I. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol. 1990 Feb;10(1):48–50. doi: 10.1097/00004714-199002000-00009. [DOI] [PubMed] [Google Scholar]
  21. Coutts R. T., Su P., Baker G. B., Daneshtalab M. Metabolism of imipramine in vitro by isozyme CYP2D6 expressed in a human cell line, and observations on metabolite stability. J Chromatogr. 1993 Jun 2;615(2):265–272. doi: 10.1016/0378-4347(93)80340-a. [DOI] [PubMed] [Google Scholar]
  22. Dahl-Puustinen M. L., Lidén A., Alm C., Nordin C., Bertilsson L. Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. Clin Pharmacol Ther. 1989 Jul;46(1):78–81. doi: 10.1038/clpt.1989.109. [DOI] [PubMed] [Google Scholar]
  23. Dahl M. L., Ekqvist B., Widén J., Bertilsson L. Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans. Acta Psychiatr Scand. 1991 Jul;84(1):99–102. doi: 10.1111/j.1600-0447.1991.tb01428.x. [DOI] [PubMed] [Google Scholar]
  24. Dahl M. L., Nordin C., Bertilsson L. Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline. Ther Drug Monit. 1991 May;13(3):189–194. doi: 10.1097/00007691-199105000-00001. [DOI] [PubMed] [Google Scholar]
  25. Desmeules J., Gascon M. P., Dayer P., Magistris M. Impact of environmental and genetic factors on codeine analgesia. Eur J Clin Pharmacol. 1991;41(1):23–26. doi: 10.1007/BF00280101. [DOI] [PubMed] [Google Scholar]
  26. Eichelbaum M. Defective oxidation of drugs: pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1982 Jan-Feb;7(1):1–22. doi: 10.2165/00003088-198207010-00001. [DOI] [PubMed] [Google Scholar]
  27. Eichelbaum M., Gross A. S. The genetic polymorphism of debrisoquine/sparteine metabolism--clinical aspects. Pharmacol Ther. 1990;46(3):377–394. doi: 10.1016/0163-7258(90)90025-w. [DOI] [PubMed] [Google Scholar]
  28. Eichelbaum M., Woolhouse N. M. Inter-ethnic difference in sparteine oxidation among Ghanaians and Germans. Eur J Clin Pharmacol. 1985;28(1):79–83. doi: 10.1007/BF00635712. [DOI] [PubMed] [Google Scholar]
  29. Evans D. A., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet. 1980 Apr;17(2):102–105. doi: 10.1136/jmg.17.2.102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Fonne-Pfister R., Bargetzi M. J., Meyer U. A. MPTP, the neurotoxin inducing Parkinson's disease, is a potent competitive inhibitor of human and rat cytochrome P450 isozymes (P450bufI, P450db1) catalyzing debrisoquine 4-hydroxylation. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1144–1150. doi: 10.1016/s0006-291x(87)80252-8. [DOI] [PubMed] [Google Scholar]
  31. Gaedigk A., Blum M., Gaedigk R., Eichelbaum M., Meyer U. A. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet. 1991 May;48(5):943–950. [PMC free article] [PubMed] [Google Scholar]
  32. Goff D. C., Midha K. K., Brotman A. W., Waites M., Baldessarini R. J. Elevation of plasma concentrations of haloperidol after the addition of fluoxetine. Am J Psychiatry. 1991 Jun;148(6):790–792. doi: 10.1176/ajp.148.6.790. [DOI] [PubMed] [Google Scholar]
  33. Gonzalez F. J., Meyer U. A. Molecular genetics of the debrisoquin-sparteine polymorphism. Clin Pharmacol Ther. 1991 Sep;50(3):233–238. doi: 10.1038/clpt.1991.131. [DOI] [PubMed] [Google Scholar]
  34. Gonzalez F. J. Molecular genetics of the P-450 superfamily. Pharmacol Ther. 1990;45(1):1–38. doi: 10.1016/0163-7258(90)90006-n. [DOI] [PubMed] [Google Scholar]
  35. Gram L. F., Debruyne D., Caillard V., Boulenger J. P., Lacotte J., Moulin M., Zarifian E. Substantial rise in sparteine metabolic ratio during haloperidol treatment. Br J Clin Pharmacol. 1989 Feb;27(2):272–275. doi: 10.1111/j.1365-2125.1989.tb05362.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Gram L. F., Overo K. F. Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. Br Med J. 1972 Feb 19;1(5798):463–465. doi: 10.1136/bmj.1.5798.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Gram L. F., Overo K., Kirk L. Influence of neuroleptics and benzodiazepines on metabolism of tricyclic antidepressants in man. Am J Psychiatry. 1974 Aug;131(8):863–866. doi: 10.1176/ajp.131.8.863. [DOI] [PubMed] [Google Scholar]
  38. Guengerich F. P., Distlerath L. M., Reilly P. E., Wolff T., Shimada T., Umbenhauer D. R., Martin M. V. Human-liver cytochromes P-450 involved in polymorphisms of drug oxidation. Xenobiotica. 1986 May;16(5):367–378. doi: 10.3109/00498258609050245. [DOI] [PubMed] [Google Scholar]
  39. Guttendorf R. J., Britto M., Blouin R. A., Foster T. S., John W., Pittman K. A., Wedlund P. J. Rapid screening for polymorphisms in dextromethorphan and mephenytoin metabolism. Br J Clin Pharmacol. 1990 Apr;29(4):373–380. doi: 10.1111/j.1365-2125.1990.tb03653.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Hammer W., Sjöqvist F. Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci. 1967 Sep 1;6(17):1895–1903. doi: 10.1016/0024-3205(67)90218-4. [DOI] [PubMed] [Google Scholar]
  41. Heim M., Meyer U. A. Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification. Lancet. 1990 Sep 1;336(8714):529–532. doi: 10.1016/0140-6736(90)92086-w. [DOI] [PubMed] [Google Scholar]
  42. Henthorn T. K., Benitez J., Avram M. J., Martinez C., Llerena A., Cobaleda J., Krejcie T. C., Gibbons R. D. Assessment of the debrisoquin and dextromethorphan phenotyping tests by gaussian mixture distributions analysis. Clin Pharmacol Ther. 1989 Mar;45(3):328–333. doi: 10.1038/clpt.1989.36. [DOI] [PubMed] [Google Scholar]
  43. Idle J. R., Smith R. L. Polymorphisms of oxidation at carbon centers of drugs and their clinical significance. Drug Metab Rev. 1979;9(2):301–317. doi: 10.3109/03602537908993896. [DOI] [PubMed] [Google Scholar]
  44. Islam S. A., Wolf C. R., Lennard M. S., Sternberg M. J. A three-dimensional molecular template for substrates of human cytochrome P450 involved in debrisoquine 4-hydroxylation. Carcinogenesis. 1991 Dec;12(12):2211–2219. doi: 10.1093/carcin/12.12.2211. [DOI] [PubMed] [Google Scholar]
  45. Kaisary A., Smith P., Jaczq E., McAllister C. B., Wilkinson G. R., Ray W. A., Branch R. A. Genetic predisposition to bladder cancer: ability to hydroxylate debrisoquine and mephenytoin as risk factors. Cancer Res. 1987 Oct 15;47(20):5488–5493. [PubMed] [Google Scholar]
  46. Kalow W. Genetics of drug transformation. Clin Biochem. 1986 Apr;19(2):76–82. doi: 10.1016/s0009-9120(86)80052-2. [DOI] [PubMed] [Google Scholar]
  47. Kalow W., Tang B. K. Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking. Clin Pharmacol Ther. 1991 Jan;49(1):44–48. doi: 10.1038/clpt.1991.8. [DOI] [PubMed] [Google Scholar]
  48. Küpfer A., Preisig R. Pharmacogenetics of mephenytoin: a new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol. 1984;26(6):753–759. doi: 10.1007/BF00541938. [DOI] [PubMed] [Google Scholar]
  49. Küpfer A., Schmid B., Preisig R., Pfaff G. Dextromethorphan as a safe probe for debrisoquine hydroxylation polymorphism. Lancet. 1984 Sep 1;2(8401):517–518. doi: 10.1016/s0140-6736(84)92591-1. [DOI] [PubMed] [Google Scholar]
  50. Llerena A., Alm C., Dahl M. L., Ekqvist B., Bertilsson L. Haloperidol disposition is dependent on debrisoquine hydroxylation phenotype. Ther Drug Monit. 1992 Apr;14(2):92–97. doi: 10.1097/00007691-199204000-00003. [DOI] [PubMed] [Google Scholar]
  51. Mellström B., Bertilsson L., Lou Y. C., Säwe J., Sjöqvist F. Amitriptyline metabolism: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther. 1983 Oct;34(4):516–520. doi: 10.1038/clpt.1983.207. [DOI] [PubMed] [Google Scholar]
  52. Mellström B., Bertilsson L., Säwe J., Schulz H. U., Sjöqvist F. E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther. 1981 Aug;30(2):189–193. doi: 10.1038/clpt.1981.147. [DOI] [PubMed] [Google Scholar]
  53. Mellström B., Säwe J., Bertilsson L., Sjöqvist F. Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. Clin Pharmacol Ther. 1986 Apr;39(4):369–371. doi: 10.1038/clpt.1986.56. [DOI] [PubMed] [Google Scholar]
  54. Mellström B., von Bahr C. Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline in human liver microsomes. Drug Metab Dispos. 1981 Nov-Dec;9(6):565–568. [PubMed] [Google Scholar]
  55. Meyer U. A., Gut J., Kronbach T., Skoda C., Meier U. T., Catin T., Dayer P. The molecular mechanisms of two common polymorphisms of drug oxidation--evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation. Xenobiotica. 1986 May;16(5):449–464. doi: 10.3109/00498258609050251. [DOI] [PubMed] [Google Scholar]
  56. Meyer U. A., Skoda R. C., Zanger U. M. The genetic polymorphism of debrisoquine/sparteine metabolism-molecular mechanisms. Pharmacol Ther. 1990;46(2):297–308. doi: 10.1016/0163-7258(90)90096-k. [DOI] [PubMed] [Google Scholar]
  57. Montgomery S. A., McAuley R., Montgomery D. B., Dawling S., Braithwaite R. A. Plasma concentration of clomipramine and desmethylclomipramine and clinical response in depressed patients. Postgrad Med J. 1980;56 (Suppl 1):130–133. [PubMed] [Google Scholar]
  58. Murray M. P450 enzymes. Inhibition mechanisms, genetic regulation and effects of liver disease. Clin Pharmacokinet. 1992 Aug;23(2):132–146. doi: 10.2165/00003088-199223020-00005. [DOI] [PubMed] [Google Scholar]
  59. Nakamura K., Goto F., Ray W. A., McAllister C. B., Jacqz E., Wilkinson G. R., Branch R. A. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985 Oct;38(4):402–408. doi: 10.1038/clpt.1985.194. [DOI] [PubMed] [Google Scholar]
  60. Nebert D. W., Nelson D. R., Adesnik M., Coon M. J., Estabrook R. W., Gonzalez F. J., Guengerich F. P., Gunsalus I. C., Johnson E. F., Kemper B. The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA. 1989 Jan-Feb;8(1):1–13. doi: 10.1089/dna.1.1989.8.1. [DOI] [PubMed] [Google Scholar]
  61. Nebert D. W., Nelson D. R., Coon M. J., Estabrook R. W., Feyereisen R., Fujii-Kuriyama Y., Gonzalez F. J., Guengerich F. P., Gunsalus I. C., Johnson E. F. The P450 superfamily: update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 1991 Jan-Feb;10(1):1–14. doi: 10.1089/dna.1991.10.1. [DOI] [PubMed] [Google Scholar]
  62. Nelson J. C., Bock J. L., Jatlow P. I. Clinical implications of 2-hydroxydesipramine plasma concentrations. Clin Pharmacol Ther. 1983 Feb;33(2):183–189. doi: 10.1038/clpt.1983.28. [DOI] [PubMed] [Google Scholar]
  63. Nelson J. C., Jatlow P., Quinlan D. M., Bowers M. B., Jr Desipramine plasma concentration and antidepressant response. Arch Gen Psychiatry. 1982 Dec;39(12):1419–1422. doi: 10.1001/archpsyc.1982.04290120049010. [DOI] [PubMed] [Google Scholar]
  64. Nelson J. C., Mazure C. M., Bowers M. B., Jr, Jatlow P. I. A preliminary, open study of the combination of fluoxetine and desipramine for rapid treatment of major depression. Arch Gen Psychiatry. 1991 Apr;48(4):303–307. doi: 10.1001/archpsyc.1991.01810280019002. [DOI] [PubMed] [Google Scholar]
  65. Nelson J. C., Mazure C., Jatlow P. I. Antidepressant activity of 2-hydroxydesipramine. Clin Pharmacol Ther. 1988 Sep;44(3):283–288. doi: 10.1038/clpt.1988.151. [DOI] [PubMed] [Google Scholar]
  66. Newton B. W., Benson R. C., McCorriston C. C. Sparteine sulfate: a potent, capricious oxytocic. Am J Obstet Gynecol. 1966 Jan 15;94(2):234–241. doi: 10.1016/0002-9378(66)90469-8. [DOI] [PubMed] [Google Scholar]
  67. Okey A. B. Enzyme induction in the cytochrome P-450 system. Pharmacol Ther. 1990;45(2):241–298. doi: 10.1016/0163-7258(90)90030-6. [DOI] [PubMed] [Google Scholar]
  68. Perault M. C., Bouquet S., Bertschy G., Vandel S., Chakroun R., Guibert S., Vandel B. Debrisoquine and dextromethorphan phenotyping and antidepressant treatment. Therapie. 1991 Jan-Feb;46(1):1–3. [PubMed] [Google Scholar]
  69. Roden D. M., Duff H. J., Altenbern D., Woosley R. L. Antiarrhythmic activity of the O-demethyl metabolite of encainide. J Pharmacol Exp Ther. 1982 Jun;221(3):552–557. [PubMed] [Google Scholar]
  70. Roy S. D., Hawes E. M., McKay G., Korchinski E. D., Midha K. K. Metabolism of methoxyphenamine in extensive and poor metabolizers of debrisoquin. Clin Pharmacol Ther. 1985 Aug;38(2):128–133. doi: 10.1038/clpt.1985.148. [DOI] [PubMed] [Google Scholar]
  71. Sarkar M. A., Hunt C., Guzelian P. S., Karnes H. T. Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos. 1992 Jan-Feb;20(1):31–37. [PubMed] [Google Scholar]
  72. Skjelbo E., Brøsen K., Hallas J., Gram L. F. The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clin Pharmacol Ther. 1991 Jan;49(1):18–23. doi: 10.1038/clpt.1991.4. [DOI] [PubMed] [Google Scholar]
  73. Spina E., Martines C., Caputi A. P., Cobaleda J., Piñas B., Carrillo J. A., Benitez J. Debrisoquine oxidation phenotype during neuroleptic monotherapy. Eur J Clin Pharmacol. 1991;41(5):467–470. doi: 10.1007/BF00626371. [DOI] [PubMed] [Google Scholar]
  74. Spina E., Steiner E., Ericsson O., Sjöqvist F. Hydroxylation of desmethylimipramine: dependence on the debrisoquin hydroxylation phenotype. Clin Pharmacol Ther. 1987 Mar;41(3):314–319. doi: 10.1038/clpt.1987.33. [DOI] [PubMed] [Google Scholar]
  75. Steiner E., Dumont E., Spina E., Dahlqvist R. Inhibition of desipramine 2-hydroxylation by quinidine and quinine. Clin Pharmacol Ther. 1988 May;43(5):577–581. doi: 10.1038/clpt.1988.76. [DOI] [PubMed] [Google Scholar]
  76. Tyndale R. F., Kalow W., Inaba T. Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). Br J Clin Pharmacol. 1991 Jun;31(6):655–660. doi: 10.1111/j.1365-2125.1991.tb05588.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wang T., Roden D. M., Wolfenden H. T., Woosley R. L., Wood A. J., Wilkinson G. R. Influence of genetic polymorphism on the metabolism and disposition of encainide in man. J Pharmacol Exp Ther. 1984 Mar;228(3):605–611. [PubMed] [Google Scholar]
  78. Wedlund P. J., Aslanian W. S., McAllister C. B., Wilkinson G. R., Branch R. A. Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin Pharmacol Ther. 1984 Dec;36(6):773–780. doi: 10.1038/clpt.1984.256. [DOI] [PubMed] [Google Scholar]
  79. Woodworth J. R., Dennis S. R., Moore L., Rotenberg K. S. The polymorphic metabolism of dextromethorphan. J Clin Pharmacol. 1987 Feb;27(2):139–143. doi: 10.1002/j.1552-4604.1987.tb02174.x. [DOI] [PubMed] [Google Scholar]
  80. Woolhouse N. M., Andoh B., Mahgoub A., Sloan T. P., Idle J. R., Smith R. L. Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther. 1979 Nov;26(5):584–591. doi: 10.1002/cpt1979265584. [DOI] [PubMed] [Google Scholar]
  81. Woolhouse N. M., Eichelbaum M., Oates N. S., Idle J. R., Smith R. L. Dissociation of co-regulatory control of debrisoquin/phenformin and sparteine oxidation in Ghanaians. Clin Pharmacol Ther. 1985 May;37(5):512–521. doi: 10.1038/clpt.1985.81. [DOI] [PubMed] [Google Scholar]
  82. Zanger U. M., Hauri H. P., Loeper J., Homberg J. C., Meyer U. A. Antibodies against human cytochrome P-450db1 in autoimmune hepatitis type II. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8256–8260. doi: 10.1073/pnas.85.21.8256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. von Bahr C., Spina E., Birgersson C., Ericsson O., Göransson M., Henthorn T., Sjöqvist F. Inhibition of desmethylimipramine 2-hydroxylation by drugs in human liver microsomes. Biochem Pharmacol. 1985 Jul 15;34(14):2501–2505. doi: 10.1016/0006-2952(85)90533-7. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Psychiatry and Neuroscience are provided here courtesy of Canadian Science Publishing

RESOURCES