Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 35, 2005 - Issue 6
89
Views
6
CrossRef citations to date
0
Altmetric
Research Article

Usefulness of hepatocytes for evaluating the genetic polymorphism of CYP2D6 substrates

&
Pages 575-587 | Received 31 Jan 2005, Published online: 22 Sep 2008

References

  • Bertilsson L, Dahl ML, Dalen P, Al-Shurbaji A. 2002. Molecular genetics of CYP2D6: Clinical relevance with focus on psychotropic drugs. British Journal of Clinical Pharmacology 53:111–122.
  • Bertz RJ, Granneman GR. 1997. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clinical Pharmacokinetics 32:210–258.
  • Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK. 1993. Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: Molecular base for interaction potential and variable disposition of active metabolites. Molecular Pharmacology 43:120–126.
  • Cai WM, Chen B, Zhou Y, Zhang YD. 1999. Fluoxetine impairs the CYP2D6-mediated metabolism of propafenone enantiomers in healthy Chinese volunteers. Clinical Pharmacology and Therapy 66:516–521.
  • Chen X, Zhong D, Blume H. 2000. Stereoselective pharmacokinetics of propafenone and its major metabolites in healthy Chinese volunteers. European Journal of Pharmacology Science 10:11–16.
  • Clarke SE, Jeffrey P. 2001. Utility of metabolic stability screening: Comparison of in vitro and in vivo clearance. Xenobiotica 31:591–598.
  • Coffman BL, King CD, Rios GR, Tephly TR. 1998. The glucuronidation of opioids, other xenobiotics, and androgens by human UGT2B7Y(268) and UGT2B7H(268). Drug Metabolism and Disposition 26:73–77.
  • Dahl-Puustinen ML, Bertilsson L. 1987. Formation of a quaternary N-glucuronide of amitriptyline in human liver microsomes. Pharmacology and Toxicology 61:342–346.
  • Dilger K, Hofmann U, Klotz U. 2000. Enzyme induction in the elderly: Effect of rifampin on the pharmacokinetics and pharmacodynamics of propafenone. Clinical Pharmacology and Therapy 67:512–520.
  • Evans EW, Relling MV. 1999. Pharmacogenomics: Translating functional genomics into rational therapeutics. Science 286:487–491.
  • Hemeryck A, De Vriendt C, Belpaire FM. 2000. Effect of selective serotonin reuptake inhibitors on the oxidative metabolism of propafenone: In vitro studies using human liver microsomes. Journal of Clinical Psychopharmacology 20:428–434.
  • Hollman M, Brode E, Hotz D, Kaumeier S, Kehrhahn OH. 1983. Investigations on the pharmacokinetics of propafenone in man. Arzneimittelforschung/Drug Research 33:763–770.
  • Ingelman-Sundberg M. 2001. Genetic susceptibility to adverse effects of drugs and environmental toxicants. The role of the CYP family of enzymes. Mutation Research 482:11–19.
  • Jones HM, Houston JB. 2004. Substrate depletion approach for determining in vitro metabolic clearance: Time dependencies in hepatocyte and microsomal incubation. Drug Metabolism and Disposition 32: 973–982.
  • Kobayashi S, Murray S, Watson D, Sesardic D, Davies DS, Boobis AR. 1989. The specificity of inhibition of debresoquine 4-hydroxylase activity by quinidine and quinine in the rat is the inverse of that in man. Biochemistry and Pharmacology 38:2795–2799.
  • Komura H, Iwaki M. 2005a. Pharmacokinetics and metabolism of metoprolol and propranolol in the female DA and female Wistar rat: The female DA rat is not always an animal model for poor metabolizers of CYP2D6. Journal of Pharmacology Science 94:397–408.
  • Komura H, Iwaki M. 2005b. Nonlinear pharmacokinetics of propafenone in rats and humans: Application of a substrate depletion assay using hepatocytes for assessment of nonlinearity. Drug Metabolism and Disposition 33:726–732.
  • Koyama E, Chiba K, Tani M, Ishizaki T. 1996. Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers. Journal of Pharmacology and Experimental Therapy 278:21–30.
  • Kroemer HK, Mikus G, Kronbach T, Meyer UA, Eichelbaum M. 1989. In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clinical Pharmacology and Therapy 45:28–33.
  • Lau YY, Sapidou E, Cui X, White RE, Cheng K-C. 2002. Development of a novel in vitro model to predict hepatic clearance using flesh, cryopreserved and sandwich-cultured hepatocytes. Drug Metabolism and Disposition 30:1446–1454.
  • Lennard MS, Jackson PR, Freestone S, Tucher GT, Ramsay LE, Woods HF. 1984. The relationship between debrisoquine oxidation phenotype and the pharmacokinetics and pharmacodynamics of propranolol. British Journal of Clinical Pharmacology 17:679–685.
  • Lewis DF, Dickins M. 2002. Substrate SARs in human P450s. Drug Discovery Today 17:918–925.
  • Masimirembwa CM, Thompson R, Andersson TB. 2001. In vitro high throughput screening of compounds for favorable metabolic properties in drug discovery. Combined Chemical High Throughput Screening 4:245–263.
  • Masubuchi Y, Hosokawa S, Hone T, Suzuki T, Ohmori S, Kitada M, Narimatsu S. 1994. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metabolism and Disposition 22:909–915.
  • McGinnity DF, Parker AJ, Soars M, Riley RJ. 2000. Automated definition of the enzymology of drug oxidation by the major human drug metabolizing cytochrome P450s. Drug Metabolism and Disposition 28:1327–1334.
  • Midha KK, Roscoe RM, Wilson TW, Cooper JK, Loo JC, Ho-Ngoc A, McGilveray IJ. 1983. Pharmacokinetics of glucuronidation of propranolol following oral administration in humans. Biopharmacology and Drug Disposition 4:331–338.
  • Nakajima M, Tane K, Nakajima S, Shimada N, Yamazaki H, Yokoi T. 2002. Evaluation of approach to predict the contribution of multiple cytochrome P450s in drug metabolism using relative activity factor: Effect of the differences in expression levels of NADPH-cytochrome P450 reductase and cytochrome b5 in the expression system and the differences in marker activities. Journal of Pharmacology Science 91:952–963.
  • Narimatsu S, Kobayashi N, Masubuchi Y, Hone T, Kakegawa T, Kobayashi H, Hardwick JP, Gonzalez FJ, Shimada N, Ohmori S, et al. 2000. Species difference in enantioselectivity for the oxidation of propranolol by cytochrome P4502D enzymes. Chemico-Biological Interactions 127:73–90.
  • Naritomi Y, Terashita S, Kagayama A, Sugiyama Y. 2003. Utility of hepatocytes in predicting drug metabolism: Comparison of hepatic intrinsic clearance in rats and humans in vivo and in vitro. Drug Metabolism and Disposition 31:580–588.
  • Obach RS, Cox LM, Tremaine LM. 2005. Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: An in vitro study. Drug Metabolism and Disposition 33:262–270.
  • Obach RS, Reed-Hagen AE. 2002. Measurement of Michaelis constants for cytochrome P450-mediated biotransformation reactions using a substrate depletion approach. Drug Metabolism and Disposition 30:831–837.
  • Raghuram TC, Koshakji RP, Wilkinson GR, Wood AJ. 1984. Polymorphic ability to metabolize propranolol alters 4-hydroxypropranolol levels but not beta blockade. Clinical Pharmacology and Therapy 36:51–56.
  • Rodrigues AD. 1997. Preclinical drug metabolism in the age of high-throughput Screening: An industrial perspective. Pharmacology Research 14:1504–1510.
  • Shimizu T, Ochiai H, ;kw11 F, Yokono Y, Kikuchi Y, Nitta M, Hama Y, Yamaguchi S, Hashimoto M, Taki K, et al. 2003. Bioinforamtics research on inter-racial difference in drug metabolism II. Analysis on relationship between enzyme activities of CYP2D6 and CYP2C19 and their relevant genotypes. Drug Metabolism and Pharmacokinetics 18:71–78.
  • Siddoway LA, Thompson KA, McAllistor CB, Wang T, Wilkinson GR, Roden DM, Woosley RL. 1987. Polymorphism of propafenone metabolism and disposition in man: Clinical and pharmacokinetic consequences. Circulation 75:785–791.
  • Sutfni TA, Perini GI, Molnar G, Jusko WJ. 1988. Multiple-dose pharmacokinetics of imipramine and its major active and conjugated metabolites in depressed patients. Journal of Clinical Psychopharmacology 8:48–53.
  • Suzuki A, Iida I, Hirota M, Akimoto M, Higuchi S, Suwa T, Tani M, Ishizaki T, Chiba K. 2003. CYP isoforms involved in the metabolism of clarithromycin in vitro: Comparison between the identification from disappearance rate and that from formation rate of metabolites. Drug Metabolism and Pharmacokinetics 18:104–113.
  • Suzuki A, Iida I, Tanaka F, Akimoto M, Fukushima K, Tani M, Ishizaki T, Chiba K. 1999. Identification of human cytochrome P-450 isoforms involved in metabolism of R(+)- and S(—)-gallopamil: Utility of in vitro disappearance rate. Drug Metabolism and Disposition 27:1254–1259.
  • Venkataktishnan K, Von Moltke LL, Greenblatt DJ. 1999. Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): Implication for interaction with enzyme-inducing drugs. Journal of Clinical Pharmacology 39:567–577.
  • Yamaoka K, Tanigawara Y, Nakagawa T, Uno T. 1981. A pharmacokinetic analysis program (multi) for microcomputer. Journal of Pharmacobiodynamics 4:879–885.
  • Yue QY, Alm C, Svensson JO, Sawe J. 1997. Quantification of the O-and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators. Therapy and Drug Monitoring 19:539–542.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.