Background. Research suggests a correlation between clozapine dose, plasma level and therapeutic response. Plasma clozapine levels may, therefore, be useful in practice. Little evidence exists, however, on the indications for, and outcome of, levels being undertaken or their use in maximum security settings. Objective. To determine if plasma clozapine levels are useful in clinical practice by analysing their use at the maximum-security State Hospital, Carstairs. Methods. All plasma clozapine levels (until March 2004) undertaken at the State Hospital, clinical indication and outcome were analysed by retrospective case note analysis. These results were compared with the published literature. Results. A total of 140 plasma clozapine levels were analysed. The average level was 0.61 mg/l and dose was 622.9 mg/day. The indications for and consequences of levels are demonstrated. A positive correlation of 0.217 was calculated. Conclusion. This paper shows that plasma clozapine levels are most useful in managing side effects and suspected non-compliance. Plasma clozapine levels are, therefore, useful in clinical practice.
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http://dx.doi.org/10.1080/13651500801983010 | DOI Listing |
J Clin Psychopharmacol
December 2024
Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Purpose/background: Clozapine is the recommended drug for treatment-resistant schizophrenia. Drug response could be affected by numerous factors such as age, sex, body mass index, co-medication, consumption of xanthine-containing beverages, smoking, and genetic variants of the enzymes involved in clozapine metabolism (CYP1A2, CYP3A4, and, to a lesser extent, CYP2C19 and CYP2D6). This study evaluated genetic and nongenetic variables that may affect clozapine plasma concentrations in Uruguayan patients with schizophrenia.
View Article and Find Full Text PDFJ Neuroinflammation
December 2024
Department of Neurosurgery, Stanford University School of Medicine, 1050 Arastradero Road, Building A, Palo Alto, Stanford, CA, 94304, United States of America.
Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and it also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer's disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through (1) chemogenetic inhibition of the locus coeruleus (LC), (2) pharmacologic blocking of β-adrenergic receptors, and (3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan.
The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations.
View Article and Find Full Text PDFTher Adv Psychopharmacol
December 2024
Department of Community Mental Health, Mental Health Service Noord-Holland Noord, Alkmaar, The Netherlands.
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