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Clozapine serum levels

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https://www.readbyqxmd.com/read/29121457/drugs-implicated-in-systemic-autoimmunity-modulate-neutrophil-extracellular-trap-formation
#1
Jorge A Irizarry-Caro, Carmelo Carmona-Rivera, Daniella M Schwartz, Sami S Khaznadar, Mariana J Kaplan, Peter C Grayson
OBJECTIVE: Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce auto-reactivity in at-risk individuals. The study objective was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation. METHODS: Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy...
November 9, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29046626/curcumin-activates-ampk-pathway-and-regulates-lipid-metabolism-in-rats-following-prolonged-clozapine-exposure
#2
Zhen Liu, Changmeng Cui, Pengfei Xu, Ruili Dang, Hualin Cai, Dehua Liao, Mengqi Yang, Qingyan Feng, Xin Yan, Pei Jiang
Clozapine (CLO) remains an ultimate option for patients with treatment resistant schizophrenia. However, the atypical antipsychotic is often associated with serious metabolic side effects, such as dyslipidemia. Hepatic sterol regulatory element-binding proteins (SREBPs) are central in the allosteric control of a variety of lipid biosynthetic pathways. There is emerging evidence that CLO can activate SREBP pathway and enhance downstream lipogenesis, whereas curcumin (CUR), a major active compound of Curcuma longa, contains hypolipidemic properties...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28948574/correlation-between-serum-concentrations-of-n-desmethylclozapine-and-granulocyte-levels-in-patients-with-schizophrenia-a-retrospective-observational-study
#3
Robert L Smith, Tore Haslemo, Ole A Andreassen, Erik Eliasson, Marja-Liisa Dahl, Olav Spigset, Espen Molden
BACKGROUND: Clozapine is restricted to use in patients with treatment-refractory schizophrenia due to the risk of a serious drop in absolute neutrophil granulocyte count (ANC). The formation of reactive, unstable metabolites (adducts) has been suggested as a mechanism of clozapine-induced granulocyte decline. These adducts are not detectable in vivo, but stable clozapine metabolites could potentially be indirect pharmacokinetic measures of adduct formation. OBJECTIVE: The present retrospective observational study investigated the correlation between concentrations of N-desmethylclozapine, the major stable clozapine metabolite, and ANC in a real-life population of clozapine-treated patients...
September 25, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28919802/abcb1-and-abcc1-single-nucleotide-polymorphisms-in-patients-treated-with-clozapine
#4
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Trudi Jones, Steven C Boyages, Mark McLean
Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response. We investigated the influence of ABCB1 rs1045642 and ABCC1 rs212090 single-nucleotide polymorphisms (SNPs) on CZ serum level, clinical outcome, and changes in body mass index (BMI) in the first year of CZ treatment...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28865402/effects-of-age-and-gender-on-the-serum-levels-of-clozapine-olanzapine-risperidone-and-quetiapine
#5
I Castberg, A A Westin, E Skogvoll, O Spigset
OBJECTIVE: To investigate serum concentrations of second-generation antipsychotics in relation to age and gender in a population ranging from 18 to 100 years. METHOD: Results from a routine therapeutic drug monitoring database were retrieved, and 43 079 samples from 11 968 patients were included (17 249 samples for clozapine, 16 171 samples for olanzapine, 5343 samples for risperidone, and 4316 samples for quetiapine). The dose-adjusted concentration was used as the primary target variable...
November 2017: Acta Psychiatrica Scandinavica
https://www.readbyqxmd.com/read/28821358/on-the-brink-of-precision-medicine-for-psychosis-treating-the-patient-not-the-disease-a-commentary-on-association-between-serum-levels-of-glutamate-and-neurotrophic-factors-and-response-to-clozapine-treatment-by-krivoy-et-al-2017
#6
https://www.readbyqxmd.com/read/28818421/erbb-signaling-antagonist-ameliorates-behavioral-deficit-induced-by-phencyclidine-pcp-in-mice-without-affecting-metabolic-syndrome-markers
#7
Hagar Tadmor, Idit Golani, Ravid Doron, Ilana Kremer, Alon Shamir
Schizophrenia is a severe syndrome that affects about 1% of the world population. Since the mid-1950s, antipsychotics have been used to treat schizophrenia with preference for treating positive symptoms; however, their tolerance level is low, there are numerous side effects, and only some patients respond to the treatment. Antipsychotic medications that are more effective, better tolerated, and with fewer adverse effects are urgently needed. Given the accumulating evidence of the role filled by the ErbB signaling network in the biology of the dopamine, GABA, and glutamate systems, and in the etiology of schizophrenia, we hypothesized that the ErbB network is a candidate for development of a novel agent through which various symptoms of schizophrenia and other psychiatric disorders might be treated...
August 14, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28664816/cyp2c19-17-protects-against-metabolic-complications-of-clozapine-treatment
#8
Irina Piatkov, Dorgival Caetano, Yolinda Assur, Sue Lynn Lau, Micheline Coelho, Trudi Jones, Tristan Nguyen, Steven Boyages, Mark McLean
OBJECTIVES: Clozapine (CZ) is the most effective drug for managing treatment-resistant schizophrenic disorders. Its use has been limited due to adverse effects, which include weight gain and new-onset diabetes, but the incidence of these varies between patients. METHODS: We investigated 187 Clozapine Clinic patients (of whom 137 consented for genotyping) for the presence of CYP2C19*17 and its association with CZ and norclozapine (NCZ) levels, and clinical outcomes...
July 18, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28643331/treatment-with-antipsychotics-in-pregnancy-changes-in-drug-disposition
#9
Andreas Austgulen Westin, Malin Brekke, Espen Molden, Eirik Skogvoll, Ingrid Castberg, Olav Spigset
Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study, we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (-76%; CI, -83%, -66%; p<0...
June 23, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28613395/clozapine-dose-for-schizophrenia
#10
REVIEW
Selvizhi Subramanian, Birgit A Völlm, Nick Huband
BACKGROUND: Schizophrenia and related disorders such as schizophreniform and schizoaffective disorder are serious mental illnesses characterised by profound disruptions in thinking and speech, emotional processes, behaviour and sense of self. Clozapine is useful in the treatment of schizophrenia and related disorders, particularly when other antipsychotic medications have failed. It improves positive symptoms (such as delusions and hallucinations) and negative symptoms (such as withdrawal and poverty of speech)...
June 14, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28599751/association-between-serum-levels-of-glutamate-and-neurotrophic-factors-and-response-to-clozapine-treatment
#11
Amir Krivoy, Eldar Hochman, Kyra-Verena Sendt, Sarah Hollander, Yael Vilner, Mirjana Selakovic, Abraham Weizman, Michal Taler
Clozapine is the only available therapy for about 30% of schizophrenia patients otherwise refractory to antipsychotics. Unfortunately, the mechanism of action of the drug is still unknown and there are no biomarkers that can predict a positive response to clozapine. We aimed to examine serum neurotrophins and glutamate levels as putative biomarkers for clozapine response based on the hypothesized mode-of-action of the compound. Blood samples of 89 chronic schizophrenia patients maintained on clozapine were analyzed in a cross-sectional design...
June 7, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28552881/vitamin-d-deficiency-and-associated-factors-in-patients-with-mental-disorders-treated-in-routine-practice
#12
Svetlana Ristic, Sandra Zivanovic, Dragan R Milovanovic, Vladimir Janjic, Danijela Djokovic, Ana Jovicevic, Marijana Stanojevic Pirkovic, Sanja Kocic
This research aimed to investigate factors associated with vitamin D deficiency and to provide data about its prevalence in patients suffering from different psychiatric illnesses. The study had a cross-sectional design and it included 220 patients of both genders, aged from 19-81 y, with a wide range of mental disorders (F00-F89), and treated in routine ambulatory and hospital practice. The researchers collected data from three sources: medical records, a study questionnaire and biochemical analysis of patients' serum samples (concentration of vitamin D measured as 25(OH)D, calcium, phosphorus, magnesium, sodium and potassium)...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/28412661/reliable-clinical-serum-analysis-with-reusable-electrochemical-sensor-toward-point-of-care-measurement-of-the-antipsychotic-medication-clozapine
#13
Mijeong Kang, Eunkyoung Kim, Thomas E Winkler, George Banis, Yi Liu, Christopher A Kitchen, Deanna L Kelly, Reza Ghodssi, Gregory F Payne
Clozapine is one of the most promising medications for managing schizophrenia but it is under-utilized because of the challenges of maintaining serum levels in a safe therapeutic range (1-3μM). Timely measurement of serum clozapine levels has been identified as a barrier to the broader use of clozapine, which is however challenging due to the complexity of serum samples. We demonstrate a robust and reusable electrochemical sensor with graphene-chitosan composite for rapidly measuring serum levels of clozapine...
September 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28340122/potential-role-of-patients-cyp3a-status-in-clozapine-pharmacokinetics
#14
Katalin Tóth, Gábor Csukly, Dávid Sirok, Ales Belic, Ádám Kiss, Edit Háfra, Máté Déri, Ádám Menus, István Bitter, Katalin Monostory
Background: The atypical antipsychotic clozapine is effective in treatment-resistant schizophrenia; however, the success or failure of clozapine therapy is substantially affected by the variables that impact the clozapine blood concentration. Thus, elucidating the inter-individual differences in clozapine pharmacokinetics can facilitate the personalized therapy. Methods: Since a potential role in clozapine metabolism is assigned to CYP1A2, CYP2C19, CYP2D6 and CYP3A enzymes, the association between the patients' CYP status (CYP genotypes, CYP expression) and clozapine clearance was evaluated in 92 psychiatric patients...
July 1, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28291036/potential-mechanisms-of-hematological-adverse-drug-reactions-in-patients-receiving-clozapine-in-combination-with-proton-pump-inhibitors
#15
REVIEW
Michał Wiciński, Mateusz M Węclewicz, Mateusz Miętkiewicz, Bartosz Malinowski, Elżbieta Grześk, Joanna Klonowska
Clozapine is a second-generation antipsychotic which has proven efficacy in treating the symptoms of schizophrenia. Although clozapine therapy is associated with a number of adverse drug reactions, it is frequently used. One of the most common adverse drug reactions is gastroesophageal reflux disease which is an indication for treatment with proton pump inhibitors (PPIs). Coadministration of clozapine and PPIs increases the risk of hematological adverse drug reactions, including neutropenia and agranulocytosis...
March 2017: Journal of Psychiatric Practice
https://www.readbyqxmd.com/read/27871032/level-of-serum-thioredoxin-and-correlation-with-neurocognitive-functions-in-patients-with-schizophrenia-using-clozapine-and-other-atypical-antipsychotics
#16
Alper Bas, Gozde Gultekin, Said Incir, Tuba Ocek Bas, Murat Emul, Alaatin Duran
Thioredoxin is a serum antioxidant that has been investigated in the etiology of schizophrenia. The aim of this study is investigating the relationship between serum thioredoxin levels and cognitive functions in acute psychotic episode and remission state patients with schizophrenia; and examining whether there were differences between patients using clozapine and other atypical antipsychotics; including risperidone, olanzapine and amisulpride. This research was performed in schizophrenia patients hospitalized with acute psychotic episode (n=57), reevaluated patients after the initiation of treatment (mean 16 weeks) (n=46), and healthy controls (n=41)...
January 2017: Psychiatry Research
https://www.readbyqxmd.com/read/27788407/determination-of-clozapine-and-five-antidepressants-in-human-plasma-serum-and-whole-blood-by-gas-chromatography-mass-spectrometry-a-simple-tool-for-clinical-and-postmortem-toxicological-analysis
#17
Vassiliki A Boumba, George Rallis, Petros Petrikis, Theodore Vougiouklakis, Venetsanos Mavreas
In this study, we describe a simple and rapid method for the determination of the antipsychotic drug clozapine and five commonly co-administered antidepressants - bupropion, mirtazapine, sertraline, clomipramine and citalopram - in serum, plasma and whole blood. Sample preparation includes solid phase extraction of analytes and determination of drug concentrations by gas chromatography-mass spectrometry without any derivatization steps. The method was fully validated according to international criteria and can be successfully applied for routine analyses...
December 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27658459/resistin-as-an-inflammatory-marker-in-patients-with-schizophrenia-treated-with-clozapine
#18
Jari-Pekka Klemettilä, Olli Kampman, Niko Seppälä, Merja Viikki, Mari Hämäläinen, Eeva Moilanen, Esa Leinonen
BACKGROUND: Schizophrenia is associated with excess cardiovascular comorbidity and mortality related to lifestyle factors, such as lack of physical activity, poor diet, and smoking. The prevalence of metabolic syndrome is increased among patients with schizophrenia, with the highest rates among patients on clozapine treatment. Smoking, obesity, physical inactivity, airway inflammation and obstruction, and adipose tissue and inflammatory marker activation are related in systemic inflammation...
February 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/27610173/negative-correlation-between-serum-s100b-and-leptin-levels-in-schizophrenic-patients-during-treatment-with-clozapine-and-risperidone-preliminary-evidence
#19
Narjes Hendouei, Seyed Hamzeh Hosseini, Amin Panahi, Zahra Khazaeipour, Fatemeh Barari, Adeleh Sahebnasagh, Shahram Ala
Recently, extensive efforts have been made to understand the rate of energy expenditure and the weight gain associated with atypical antipsychotic treatment, including identification of markers of obesity risk. In recent years, leptin, an adipocyte hormone, has gained significant interest in psychiatric disorders. S100B has been considered as a surrogate marker for astrocyte-specific damage in neurologic disorders. Also, S100B has been detected in adipose with concentration as high as nervous tissue as a second release source...
2016: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/27606316/inflammatory-cytokines-and-antipsychotic-induced-weight-gain-review-and-clinical-implications
#20
REVIEW
Trehani M Fonseka, Daniel J Müller, Sidney H Kennedy
Antipsychotic medications (APs), particularly second-generation APs, are associated with significant weight gain in schizophrenia patients. Recent evidence suggests that the immune system may contribute to antipsychotic-induced weight gain (AIWG) via AP-mediated alterations of cytokine levels. Antipsychotics with a high propensity for weight gain, such as clozapine and olanzapine, influence the expression of immune genes, and induce changes in serum cytokine levels to ultimately down-regulate neuroinflammation...
May 2016: Molecular Neuropsychiatry
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