TITLE

Cytochrome P450 Phenotyping/Genotyping in Patients Receiving Antipsychotics: Useful Aid to Prescribing?

AUTHOR(S)
Dahl, M-L.
PUB. DATE
May 2002
SOURCE
Clinical Pharmacokinetics;May2002, Vol. 41 Issue 7, p453
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Many antipsychotics, including perphenazine, zuclopenthixol, thioridazine, haloperidol and risperidone, are metabolised to a significant extent by the polymorphic cytochrome P450 (CYP) 2D6, which shows large interindividual variation in activity. Significant relationships between CYP2D6 genotype and steady-state concentrations have been reported for perphenazine, zuclopenthixol, risperidone and haloperidol when used in monotherapy. Other CYPs, especially CYP1A2 and CYP3A4, also contribute to the interindividual variability in the kinetics of antipsychotics and the occurrence of drug interactions. For many antipsychotics, the role of the different CYPs at therapeutic drug concentrations remains to be clarified. Some studies have suggested that poor metabolisers for CYP2D6 would be more prone to oversedation and possibly parkinsonism during treatment with classical antipsychotics, whereas other, mostly retrospective, studies have been negative or inconclusive. For the newer antipsychotics, such data are lacking. Whether phenotyping or genotyping for CYP2D6 or other CYPs can be used to predict an optimal dose range has not been studied so far. Genotyping or phenotyping can today be recommended as a complement to plasma concentration determination when aberrant metabolic capacity (poor or ultrarapid) of CYP2D6 substrates is suspected. The current rapid developments in molecular genetic methodology and pharmacogenetic knowledge can in the near future be expected to provide new tools for prediction of the activity of the various drug-metabolising enzymes. Further prospective clinical studies in well-defined patient populations and with adequate evaluation of therapeutic and adverse effects are required to establish the potential of pharmacogenetic testing in clinical psychiatry.
ACCESSION #
6878790

 

Related Articles

  • Effects of CYP3A Inhibition on the Metabolism of Cilostazol. Suri, A.; Forbes, W.P.; Bramer, S.L. // Clinical Pharmacokinetics;1999 Supplement, Vol. 37 Issue 6, p61 

    Objective: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A and 2C19. This study investigated the role of CYP3A inhibition on the metabolism of cilostazol. Design: The study was conducted as a single-centre, open-label, nonrandomised,...

  • Cytochrome P450 in the Brain ; A Review. Hedlund, E.; Gustafsson, J.A.; Warner, M. // Current Drug Metabolism;Sep2001, Vol. 2 Issue 3, p245 

    After many frustrating decades of unsuccessful attempts to characterize the isoforms of P450 in the brain, several scientific breakthroughs in the 80s and 90s have resulted in major advances in our understanding of cytochromes P450 (CYP) in brain. We now know that classical CYP inducers, e.g....

  • Effect of Omeprazole on the Metabolism of Cilostazol. Suri, A.; Bramer, S.L. // Clinical Pharmacokinetics;1999 Supplement, Vol. 37 Issue 6, p53 

    Objective: In vitro results suggest that cilostazol is metabolised by cytochrome P450 (CYP) isoforms 1A2, 2D6, 3A4 and 2C19. This study was designed to evaluate the effect of concomitant administration of omeprazole (a CYP2C19 inhibitor) on the pharmacokinetics of a single 100mg oral dose of...

  • Metabolism Profiling, and Cytochrome P450 Inhibition & Induction in Drug Discovery. Zhengin Yan, Thomas C.; Caldwell, Gary W. // Current Topics in Medicinal Chemistry;Nov2001, Vol. 1 Issue 5, p403 

    To reduce the high attrition rates of NCEs in preclinical and clinical development uncovering pharmacokinetics, toxicokinetics, drug metabolism, and drug-drug interactions early in drug discovery would be highly valuable. There have been many in vitro screens developed for these areas that have...

  • Atypical Enzyme Kinetics: Their Effect on In Vitro-In Vivo Pharmacokinetic Predictions and Drug Interactions. Tracy, Timothy S. // Current Drug Metabolism;Oct2003, Vol. 4 Issue 5, p341 

    The most common method for estimating a drug's in vivo clearance from in vitro data has involved using the classical Michaelis-Menten model to describe the observed in vitro data and from this estimate intrinsic clearance. This process assumes that the drug obeys standard enzyme kinetics that...

  • Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Dresser, G.K.; Spence, J.D.; Bailey, D.G. // Clinical Pharmacokinetics;2000, Vol. 38 Issue 1, p41 

    Drug interactions occur when the efficacy or toxicity of a medication is changed by administration of another substance. Pharmacokinetic interactions often occur as a result of a change in drug metabolism. Cytochrome P450 (CYP) 3A4 oxidises a broad spectrum of drugs by a number of metabolic...

  • Cytochrome P450 drug interactions within the HMG-CoA reductase inhibitor class: are they clinically relevant? Martin, J.; Krum, H.; Martin, Jennifer; Krum, Henry // Drug Safety;Jan2003, Vol. 26 Issue 1, p13 

    The present review outlines the clinical relevance of pharmacokinetic drug interactions within the HMG-CoA reductase inhibitor class. These interactions can result in markedly increased or decreased plasma concentrations of some drugs within this class. However, the relationship between altered...

  • Pharmacokinetics of Haloperidol. Kudo, Shoji; Ishizaki, Takashi // Clinical Pharmacokinetics;1999, Vol. 37 Issue 6, p435 

    Haloperidol is commonly used in the therapy of patients with acute and chronic schizophrenia. The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP), carbonyl reductase and uridine diphosphoglucose glucuronosyltransferase. The greatest proportion of the...

  • Investigation of the mutual pharmacokinetic interactions between bosentan, a dual endothelin receptor antagonist, and simvastatin. Dingemanse, J.; Schaarschmidt, D.; van Giersbergen, P.L.M.; Dingemanse, Jasper; Schaarschmidt, Dieter; van Giersbergen, Paul L M // Clinical Pharmacokinetics;Feb2003, Vol. 42 Issue 3, p293 

    Background: In vitro, bosentan has been shown to be a mild inducer of cytochrome P450 (CYP) 2C9 and 3A4.Purpose: To investigate in vivo the mutual pharmacokinetic interactions between bosentan and simvastatin, a CYP3A4 substrate.Methods: Nine healthy male...

  • Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Brenner, S.S.; Herrlinger, C.; Dilger, K.; Murdter, T.E.; Hofmann, U.; Marx, C.; Klotz, U.; Brenner, Stefanie S; Herrlinger, Charlotte; Dilger, Karin; M├╝rdter, Thomas E; Hofmann, Ute; Marx, Claudia; Klotz, Ulrich // Clinical Pharmacokinetics;Feb2003, Vol. 42 Issue 3, p283 

    Objective: To analyse the influence of age and cytochrome P450 (CYP) 2C9 genotype on the steady-state disposition of the standard NSAID diclofenac and the new COX-2 selective inhibitor celecoxib, both of which are metabolised by the polymorphically expressed CYP2C9.Design:...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics