Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid
Само за регистроване кориснике
2023
Аутори
Panić, BojanaJovanović, Marija
Lukić, Vera
Vučićević, Katarina
Miljković, Branislava
Milovanović, Srđan
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant ...effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.
Кључне речи:
Clozapine / Drug monitoring / Metabolism / Norclozapine / Pharmacokinetic variability / ValproateИзвор:
European Journal of Clinical Pharmacology, 2023Издавач:
- Springer
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
DOI: 10.1007/s00228-023-03569-2
ISSN: 0031-6970
PubMed: 37733278
Scopus: 2-s2.0-85171689044
Институција/група
PharmacyTY - JOUR AU - Panić, Bojana AU - Jovanović, Marija AU - Lukić, Vera AU - Vučićević, Katarina AU - Miljković, Branislava AU - Milovanović, Srđan PY - 2023 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5040 AB - Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant. PB - Springer T2 - European Journal of Clinical Pharmacology T1 - Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid DO - 10.1007/s00228-023-03569-2 ER -
@article{ author = "Panić, Bojana and Jovanović, Marija and Lukić, Vera and Vučićević, Katarina and Miljković, Branislava and Milovanović, Srđan", year = "2023", abstract = "Purpose: The goal of the study was to examine clozapine (CLZ) and norclozapine (NCLZ) therapeutic drug monitoring (TDM) data and associated sources of pharmacokinetic variability, particularly the impact of valproic acid (VPA) use. Methods: This study included 126 patients with psychiatric disorders on mono- or co-therapy with CLZ. Patients’ data during routine TDM were collected retrospectively from clinical records. The descriptive and statistical analysis was computed using IBM SPSS Statistics software (version 22, NY, USA). Multiple linear regression, based on the last observations, was used to assess correlation between demographic characteristics, life habits and co-therapy with dose-corrected serum levels (C/D) of CLZ and NCLZ, as well as CLZ/NCLZ. Results: A total of 295 CLZ concentrations were measured in 126 patients, with a mean of 275.5 ± 174.4 µg/L, while 124 NCLZ concentrations were determined in 74 patients, with a mean of 194.6 ± 149.8 µg/L. A statistically significant effect on ln-transformed CLZ C/D was confirmed for sex and smoking, whereas sex, smoking and VPA therapy were associated with ln-transformed NCLZ C/D. According to the final models, lower values of NCLZ C/D for about 45.9% can be expected in patients receiving VPA. Concomitant use of VPA was the only factor detected to contribute in CLZ/NCLZ variability. Conclusion: The results of this study may help clinicians interpret TDM data and optimize CLZ dosing regimens, especially in patients concomitantly treated with VPA. Our results show that VPA primarily decreases NCLZ levels, while alteration of the parent drug is not statistically significant.", publisher = "Springer", journal = "European Journal of Clinical Pharmacology", title = "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid", doi = "10.1007/s00228-023-03569-2" }
Panić, B., Jovanović, M., Lukić, V., Vučićević, K., Miljković, B.,& Milovanović, S.. (2023). Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology Springer.. https://doi.org/10.1007/s00228-023-03569-2
Panić B, Jovanović M, Lukić V, Vučićević K, Miljković B, Milovanović S. Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid. in European Journal of Clinical Pharmacology. 2023;. doi:10.1007/s00228-023-03569-2 .
Panić, Bojana, Jovanović, Marija, Lukić, Vera, Vučićević, Katarina, Miljković, Branislava, Milovanović, Srđan, "Association of clozapine and norclozapine levels with patient and therapy characteristics—focus on interaction with valproic acid" in European Journal of Clinical Pharmacology (2023), https://doi.org/10.1007/s00228-023-03569-2 . .