Marit Tveito1,2, Robert Løvsletten Smith3, Espen Molden3,4, Gudrun Høiseth3,5,6. 1. Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85, Vinderen, 0319, Oslo, Norway. marit.tveito@me.com. 2. Norwegian National Advisory Unit on Aging and Health, Vestfold Hospital Trust, Tønsberg, Norway. marit.tveito@me.com. 3. Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85, Vinderen, 0319, Oslo, Norway. 4. Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway. 5. Department of Forensic Sciences, Oslo University Hospital, Oslo, Norway. 6. Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Abstract
PURPOSE: Zuclopenthixol is an antipsychotic available as oral and long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age on zuclopenthixol exposure during oral and LAI administrations without and with adjustment for CYP2D6 genotype. METHODS: Data on serum concentrations of zuclopenthixol and CYP2D6 genotype (available for 28.2% of the population) from patients using oral or LAI zuclopenthixol were included retrospectively from a therapeutic drug monitoring service during the period 2005-2019. As a measure of exposure, dose-adjusted serum concentration (C/D ratio) was used. Based on age, patients were grouped to older (≥ 65 years) or younger (18-64 years). Linear mixed model analyses without and with adjustment for CYP2D6 genotype were used. RESULTS: Serum concentrations of zuclopenthixol from 1145 (14.1% older) and 899 patients (24.6% older) in the LAI and oral groups were included, respectively. Compared with younger patients, older patients had a higher C/D ratio of zuclopenthixol for LAI (+ 25-33%, p < 0.001) and oral formulation (+ 25-29%, p ≤ 0.003) without and with adjustment for CYP2D6 genotype. The doses were lower in older versus younger patients (oral: - 30%; LAI: - 20%; p < 0.001). Compared with the younger LAI users without reduced CYP2D6 function, a higher C/D ratio was observed in the older LAI users with reduced CYP2D6 function (+ 104%, p < 0.001). CONCLUSION: The present study showed that zuclopenthixol exposure increases in older patients and that the older LAI users with reduced CYP2D6 function are exposed to high serum concentrations. Also, the present study showed that similar dose reductions are required for oral and LAI users.
PURPOSE:Zuclopenthixol is an antipsychotic available as oral and long-acting injectable (LAI) formulations. The aim of this study was to investigate the effect of age on zuclopenthixol exposure during oral and LAI administrations without and with adjustment for CYP2D6 genotype. METHODS: Data on serum concentrations of zuclopenthixol and CYP2D6 genotype (available for 28.2% of the population) from patients using oral or LAI zuclopenthixol were included retrospectively from a therapeutic drug monitoring service during the period 2005-2019. As a measure of exposure, dose-adjusted serum concentration (C/D ratio) was used. Based on age, patients were grouped to older (≥ 65 years) or younger (18-64 years). Linear mixed model analyses without and with adjustment for CYP2D6 genotype were used. RESULTS: Serum concentrations of zuclopenthixol from 1145 (14.1% older) and 899 patients (24.6% older) in the LAI and oral groups were included, respectively. Compared with younger patients, older patients had a higher C/D ratio of zuclopenthixol for LAI (+ 25-33%, p < 0.001) and oral formulation (+ 25-29%, p ≤ 0.003) without and with adjustment for CYP2D6 genotype. The doses were lower in older versus younger patients (oral: - 30%; LAI: - 20%; p < 0.001). Compared with the younger LAI users without reduced CYP2D6 function, a higher C/D ratio was observed in the older LAI users with reduced CYP2D6 function (+ 104%, p < 0.001). CONCLUSION: The present study showed that zuclopenthixol exposure increases in older patients and that the older LAI users with reduced CYP2D6 function are exposed to high serum concentrations. Also, the present study showed that similar dose reductions are required for oral and LAI users.
Authors: Jari Tiihonen; Ellenor Mittendorfer-Rutz; Maila Majak; Juha Mehtälä; Fabian Hoti; Erik Jedenius; Dana Enkusson; Amy Leval; Jan Sermon; Antti Tanskanen; Heidi Taipale Journal: JAMA Psychiatry Date: 2017-07-01 Impact factor: 21.596
Authors: S J C Davies; A A Westin; I Castberg; G Lewis; M S Lennard; S Taylor; O Spigset Journal: Acta Psychiatr Scand Date: 2010-10-12 Impact factor: 6.392