Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies

@article{Davies2010CharacterisationOZ,
  title={Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies},
  author={S J Davies and Andreas Austgulen Westin and Ingrid Castberg and G. Lewis and Martin S. Lennard and S Taylor and Olav Spigset},
  journal={Acta Psychiatrica Scandinavica},
  year={2010},
  volume={122}
}
Davies SJC, Westin AA, Castberg I, Lewis G, Lennard MS, Taylor S, Spigset O. Characterisation of zuclopenthixol metabolism by in vitro and therapeutic drug monitoring studies. 
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Authors C. Hiemke, N. Bergemann, H. Zurek, and G. Baumann write about life in the post-war period and the aftermath of the Second World War, as well as some of the events leading up to and during the conflict.
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References

SHOWING 1-10 OF 27 REFERENCES
The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol
TLDR
This study evaluates the importance of the CYP2D6 genotype for the disposition of the neuroleptic agents perphenazine and zuclopenthixol.
Recent Developments in Drug Metabolism of Relevance to Psychiatrists
  • B. Pollock
  • Medicine
    Harvard review of psychiatry
  • 1994
TLDR
Preliminary findings from the author's studies of P450 2D6 phenotyping in elderly patients treated with nortriptyline and perphenazine are reported, which may lead to earlier identification of patients at risk because of atypical drug metabolism.
Disposition of the neuroleptic zuclopenthixol cosegregates with the polymorphic hydroxylation of debrisoquine in humans
TLDR
The study indicates that the disposition of zuclopenthixol, as well as that of perphenazine, is related to the genetically determined capacity to hydroxylate debrisoquine, and the significance of this polymorphism for the clinical use of neuroleptics is discussed.
Influence of Cyp2D6 genetic polymorphism on ratios of steady-state serum concentration to dose of the neuroleptic zuclopenthixol.
TLDR
It is considered that TDM adequately takes into account dose adjustments for both EM and PM subjects in the context of this neuroleptic zuclopenthixol, and is likely to be effective in patients receiving potentially interacting drugs.
Maintenance therapy with zuclopenthixol decanoate: associations between plasma concentrations, neurological side effects and CYP2D6 genotype
TLDR
The higher zuclopenthixol steady-state plasma concentrations in heterozygous EM and PM schizophrenic patients receiving monotherapy with z EuclopenthIXol-decanoate than in homozygous EMs indicates a significant role of CYP2D6 in the systemic elimination of zuclanethixol.
Comparison of the kinetic interactions of the neuroleptics perphenazine and zuclopenthixol with tricyclic antidepressives.
  • K. Linnet
  • Chemistry, Medicine
    Therapeutic drug monitoring
  • 1995
TLDR
Perphenazine increases the concentration of tricyclic antidepressives to a moderate extent and zuclopenthixol does not exert any impact under routine therapeutic drug monitoring, even though the drug is known to partly depend on metabolism by the isozyme cytochrome P450 2D6.
Characterization of the common genetic defect in humans deficient in debrisoquine metabolism
TLDR
It is shown that poor meta-bolizers have negligible amounts of the cytochrome P450 enzyme P450dbl, providing a molecular explanation for one of man's most commonly defective genes.
Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9.
TLDR
Ketoconazole and sulphaphenazole can be used to establish the involvement of P4503A and 2C9 respectively in oxidative reactions in human liver microsomes and demonstrate an inhibitory effect on cyclosporine oxidase and testosterone 6 beta-hydroxylase activities.
Carbamazepine treatment induces the CYP3A4 catalysed sulphoxidation of omeprazole, but has no or less effect on hydroxylation via CYP2C19.
TLDR
The induction of the sulphoxidation of omeprazole by CBZ seems to have no major clinical implication, and the ratio of the AUCs of omEPrazole and its sulphone, used as an index of CYP3A4 activity, decreased in all patients.
Determination of zuclopenthixol and its main N-dealkylated metabolite in biological fluids using high-performance liquid chromatography with post-column photochemical derivatization and fluorescence detection.
TLDR
A highly sensitive high-performance liquid chromatographic (HPLC) method for the assay of cis-(Z)-clopenthixol (zuclop tenthixol) in urine and plasma has been developed and is very suitable for study of the photochemical reaction, since the chloro-thioxanth one and thioxanthone are well separated from the isomers of clopenthIXol.
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