Steady-State Clozapine and Norclozapine Pharmacokinetics in Maori and European Patients
| Autor: | Frederic Lam, Paul Glue, Chris Gale, C.T. Hung, Noelyn Hung, David B Menkes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Drug
Adult Male Bioavailability media_common.quotation_subject Cmax Pharmacokinetic lcsh:Medicine Pharmacology General Biochemistry Genetics and Molecular Biology White People Cmax maximum plasma concentration Maori 03 medical and health sciences Cmin Young Adult 0302 clinical medicine Pharmacokinetics medicine Ethnicity Humans Clozapine Cmin minimum plasma concentration media_common Norclozapine lcsh:R5-920 business.industry lcsh:R AUC0 − τ area under the curve from time 0 to the end of the dosing interval General Medicine Middle Aged medicine.disease 030227 psychiatry Metabolism Schizophrenia Toxicity Female business lcsh:Medicine (General) tmax time to Cmax 030217 neurology & neurosurgery medicine.drug Research Paper |
| Zdroj: | EBioMedicine, Vol 27, Iss C, Pp 134-137 (2018) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | 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 24 h 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. Highlights • Metabolism of clozapine, our most effective antipsychotic drug, was compared in New Zealand's two main ethnic groups. • Clozapine pharmacokinetic parameters were similar in Maori and European patients. • Accordingly, clozapine dosing does not need to take Maori or European ethnicity into account. Clozapine is an essential medicine for treatment-resistant schizophrenia, but its use is limited by significant side-effects. We were interested to see if Maori and European patients in New Zealand differed in terms of clozapine pharmacokinetics, as this could influence both clinical response and side-effects. We found essentially no difference in clozapine pharmacokinetics between these groups, meaning that dosing decisions can be made based on clinical factors without regard to ethnicity. |
| Databáze: | OpenAIRE |
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