Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations

Journal of Clinical Pharmacology

Volumn 41, Issue 8, 2001, Pages 823-832

  Olesen, O V ^a   Linnet, K ^a  

^a AARHUS UNIVERSITY HOSPITAL   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CLOZAPINE; CYTOCHROME P450; CYTOCHROME P450 1A2; CYTOCHROME P450 2C19; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4;

ARTICLE; DEMETHYLATION; DRUG METABOLISM; ENZYME KINETICS; LIVER MICROSOME; PROTEIN EXPRESSION;

ANTIPSYCHOTIC AGENTS; ARYL HYDROCARBON HYDROXYLASES; CLOZAPINE; CYTOCHROME P-450 CYP1A2; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 ENZYME SYSTEM; DEALKYLATION; HUMANS; MICROSOMES, LIVER; MIXED FUNCTION OXYGENASES; STEROID 16-ALPHA-HYDROXYLASE; STEROID HYDROXYLASES;

EID: 0034925896     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1177/00912700122010717     Document Type: Article

References (40)

1. Clozapine: A novel antipsychotic agent
2. Pharmacokinetics and pharmacodynamics of clozapine
3. Clozapine-induced agranulocytosis: Incidence and factors in the United States
4. Clozapine: A review of its pharmacological properties, and therapeutic use in schizophrenia
5. Clinical pharmacokinetics of clozapine in chronic schizophrenic patients
6. Single- vs multiple-dose pharmacokinetics of clozapine in psychiatric patients
7. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine
8. Metabolism of clozapine by-cDNA-expressed human cytochrome P450 enzymes
9. Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine
10. Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine
11. Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic
12. Metabolism and bioactivation of clozapine by human liver in vitro
13. The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6
14. Therapeutic drug monitoring of clozapine treatment: Therapeutic threshold value for serum clozapine concentrations
15. Fluvoxamine-clozapine drug interaction: Inhibition in vitro of five cytochrome P450 isoforms involved in clozapine metabolism
16. Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver microsomes: Application of the relative activity factor approach
17. Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man
18. Cytochrome P450 inhibitors: Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes
19. Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9
20. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes
21. Assessment of specificity of eight chemical inhibitors using cDNA-expressed cytochromes P450
22. Disposition of clozapine in man: Lack of association with debrisoquine and S-mephenytoin hydroxylation polymorphisms
23. Influence of patient-related variables on clozapine plasma levels
24. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: Effect of smoking
25. Clozapine serum concentrations are lower in smoking than in non-smoking schizophrenic patients
26. Effects of caffeine withdrawal from the diet on the metabolism of clozapine in schizophrenic patients
27. Effect of caffeine on clozapine pharmacokinetics in healthy volunteers
28. Elevated levels of clozapine in serum after addition of fluvoxamine
29. Fluvoxamine increases the clozapine serum levels significantly
30. Serious drug interaction between clozapine-leponex and fluvoxamine-fevarin
31. In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine
32. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: Differential effects of fluvoxamine and paroxetine in a prospective study
33. Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test
34. Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole
35. Absence of interaction between erythromycin and a single dose of clozapine
36. Plasma levels of clozapine and desmethylclozapine are unaffected by concomitant ingestion of grapefruit juice
37. Merits and limitations of recombinant models for the study of human P450-mediated drug metabolism and toxicity: An intralaboratory comparison
38. Biotransformation of clozapine in humans
39. Pharmacokinetics of clozapine and its metabolites in psychiatric patients: Plasma protein binding and renal clearance