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EBioMedicine. 2018 Jan;27:134-137. doi: 10.1016/j.ebiom.2017.11.030. Epub 2017 Dec 13.

Steady-State Clozapine and Norclozapine Pharmacokinetics in Maori and European Patients.

Author information

1
Waikato Clinical Campus, Private Bag 3200, Hamilton, New Zealand. Electronic address: david.menkes@auckland.ac.nz.
2
University of Otago, PO Box 56, Dunedin 9054, New Zealand. Electronic address: paul.glue@otago.ac.nz.
3
University of Otago, PO Box 56, Dunedin 9054, New Zealand. Electronic address: chris.gale@otago.ac.nz.
4
Zenith Technology, 156 Frederick Street, Dunedin 9016, New Zealand. Electronic address: fred.lam@zenithtechnology.co.nz.
5
Zenith Technology, 156 Frederick Street, Dunedin 9016, New Zealand. Electronic address: tak.hung@zenithtechnology.co.nz.
6
Zenith Technology, 156 Frederick Street, Dunedin 9016, New Zealand. Electronic address: noelyn.hung@otago.ac.nz.

Abstract

BACKGROUND:

Clozapine is the most effective drug for treatment-resistant schizophrenia, but its use is limited by toxicity. Because ethnicity has been reported to affect clozapine metabolism, we compared its steady state pharmacokinetics in New Zealand Maori and European patients.

METHODS:

Clozapine and norclozapine steady state bioavailability was assessed over 24h under fasting and fed conditions in 12 Maori and 16 European patients treated for chronic psychotic illnesses with stable once-daily clozapine doses. Plasma clozapine and norclozapine concentrations were assessed using liquid chromatography with tandem mass spectrometry; pharmacokinetic parameters were calculated using standard non-compartmental methods, and compared using unpaired t-tests.

FINDINGS:

Mean pharmacokinetic parameters (AUC, Cmax and Cmin) for clozapine and norclozapine were virtually identical in Maori and European subjects, under both fed and fasted conditions.

DISCUSSION:

Clozapine bioavailability does not vary between Maori and European patients, and thus does not need to be considered in prescribing decisions. Additional studies are needed to identify if there are differences between Maori and European populations for drugs metabolized by other enzyme pathways.

KEYWORDS:

Bioavailability; Clozapine; Maori; Metabolism; Norclozapine; Pharmacokinetic

PMID:
29254680
PMCID:
PMC5828556
DOI:
10.1016/j.ebiom.2017.11.030
[Indexed for MEDLINE]
Free PMC Article

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