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British Journal of Clinical Pharmacology Feb 2021The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme.
AIMS
The aim of this study was to evaluate the population pharmacokinetics (PopPK) of olanzapine in children and devise a model-informed paediatric dosing scheme.
METHODS
The PopPK of olanzapine was characterized using opportunistically collected plasma samples from children receiving olanzapine per standard of care for any indication. A nonlinear mixed effect modelling approach was employed for model development using the software NONMEM (v7.4). Simulations from the developed PopPK model were used to devise a paediatric dosing scheme that targeted comparable plasma exposures to adolescents and adults.
RESULTS
Forty-five participants contributed 83 plasma samples towards the analysis. The median (range) postnatal age and body weight of participants were 3.8 years (0.2-19.2) and 14.1 kg (4.2-111.7), respectively. The analysis was restricted to pharmacokinetic (PK) samples collected following enteral administration (oral and feeding tube). A one-compartment model with linear elimination provided an appropriate fit to the data. The final model included the covariates body weight and postmenstrual age (PMA) on apparent olanzapine clearance (CL/F). Typical CL/F and apparent volume of distribution (scaled to 70 kg) were 16.8 L/h (21% RSE) and 663 L (13% RSE), respectively. Developed dosing schemes used weight-normalized doses for children ≤6 months postnatal age or <15 kg and fixed doses for children ≥15 kg.
CONCLUSION
We developed a paediatric PopPK model for enterally-administered olanzapine. To our knowledge, this analysis is the first study to characterize the PK of olanzapine in participants ranging from infants to adolescents. Body weight and PMA were identified as influential covariates for characterizing developmental changes in olanzapine apparent clearance.
Topics: Adolescent; Adult; Child; Humans; Infant; Models, Biological; Nonlinear Dynamics; Olanzapine
PubMed: 32497307
DOI: 10.1111/bcp.14414 -
Australasian Psychiatry : Bulletin of... Dec 2018Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper... (Review)
Review
OBJECTIVES:
Switching between different antipsychotic therapies is a frequent occurrence in the management of patients with schizophrenia and other psychotic disorders. This paper provides a review of the principles of antipsychotic switching and discusses pharmacological principles underlying adverse events that occur while switching olanzapine to another antipsychotic medication. It offers suggestions for management of switch-associated adverse events in clinical settings.
CONCLUSIONS:
Few publications explore olanzapine switch-related adverse events, the underlying pharmacological principles and appropriate switching strategies to minimise the risk of adverse events. There is still a need for further studies to verify existing knowledge and assist in the development of 'gold standard' guidelines that outline appropriate switching strategies and duration of the switching process to reduce and avoid adverse events.
Topics: Antipsychotic Agents; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; Humans; Olanzapine; Psychotic Disorders; Schizophrenia
PubMed: 30407073
DOI: 10.1177/1039856218810166 -
The Annals of Pharmacotherapy Aug 2019The purpose of this review is to summarize the current evidence of the off-label use of intravenous (IV) olanzapine and discuss its risks versus benefits for the... (Review)
Review
The purpose of this review is to summarize the current evidence of the off-label use of intravenous (IV) olanzapine and discuss its risks versus benefits for the management of agitation. : A literature search was conducted to gather relevant data regarding IV use of olanzapine for the management of acute agitation. PubMed, EMBASE, MEDLINE, and IPA were searched using the keywords and MESH terms: , and . : All case reports, and retrospective and prospective studies evaluating the efficacy and safety of IV olanzapine administration for agitation from January 2004 to December 2018 were analyzed. : Doses from 2.5 to 10 mg given as an IV bolus (maximum dose of 30 mg/d) have been administered. Rescue medications such as droperidol or parenteral benzodiazepines are sometimes coadministered to assist with achieving adequate sedation. Prospective studies demonstrate efficacy similar to droperidol in achieving adequate sedation within 10 minutes and similar time to onset of sedation. Rates of respiratory depression and airway obstruction are low and similar to that of comparative agents, including intramuscular olanzapine. This review evaluated the off-label use of IV olanzapine to manage agitation based on case reports, and retrospective and prospective data. : The use of IV olanzapine remains controversial in the absence of clear evidence evaluating safety and efficacy. Future studies are warranted comparing IV olanzapine with more commonly utilized and Food and Drug Administration-approved treatment modalities for acute agitation in the emergency department and other settings.
Topics: Antipsychotic Agents; Humans; Injections, Intravenous; Male; Off-Label Use; Olanzapine; Psychomotor Agitation; Treatment Outcome; United States
PubMed: 30758221
DOI: 10.1177/1060028019831634 -
Microbiology Spectrum Aug 2023Olanzapine is one of the most effective medicines available for stabilizing schizophrenia spectrum disorders. However, it has been reported to show the greatest...
Olanzapine is one of the most effective medicines available for stabilizing schizophrenia spectrum disorders. However, it has been reported to show the greatest propensity for inducing body weight gain and producing metabolic side effects, which cause a great burden in patients with psychiatric disorders. Since the gut microbiota has a profound impact on the initiation and development of metabolic diseases, we conducted a longitudinal study to explore its role in olanzapine-induced obesity and metabolic abnormalities. Female Sprague-Dawley rats were treated with different doses of olanzapine, and metabolic and inflammatory markers were measured. Olanzapine significantly induced body weight gain (up to a 2.1-fold change), which was accompanied by hepatic inflammation and increased plasma triglyceride levels (up to a 2.9-fold change), as well as gut microbiota dysbiosis. Subsequently, fuzzy c-means clustering was used to characterize three clusters of longitudinal trajectories for microbial fluctuations: (i) genera continuing to increase, (ii) genera continuing to decrease, and (iii) genera temporarily changing. Among them, ( = 0.38), ( = 0.43), and UCG-001 ( = 0.52) positively correlated with body weight gain. In addition, two MetaCyc metabolic pathways were identified as associated with olanzapine-induced body weight gain, including the superpathway of glucose and xylose degradation and the superpathway of l-threonine biosynthesis. In conclusion, we demonstrate that olanzapine can directly alter the gut microbiota and rapidly induce dysbiosis, which is significantly associated with body weight gain. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by olanzapine. Olanzapine is one of the most effective second-generation antipsychotics for stabilizing schizophrenia spectrum disorders. However, olanzapine has multiple drug-induced metabolic side effects, including weight gain. This study provides insight to the gut microbiota target in olanzapine-induced obesity. Specifically, we explored the longitudinal gut microbiota trajectories of female Sprague-Dawley rats undergoing olanzapine treatment. We showed that olanzapine treatment causes a dynamic alteration of gut microbiota diversity. Additionally, we identified three genera, , , and UCG-001, that may play an important role in olanzapine-induced obesity. In this case, the supply or removal of specific elements of the gut microbiota may represent a promising avenue for treatment of olanzapine-related metabolic side effects.
Topics: Rats; Animals; Female; Olanzapine; Rats, Sprague-Dawley; Gastrointestinal Microbiome; Dysbiosis; Longitudinal Studies; Weight Gain; Obesity
PubMed: 37260381
DOI: 10.1128/spectrum.00058-23 -
Postgraduate Medical Journal Nov 2022
Topics: Humans; Olanzapine; Myocarditis; Rhabdomyolysis; Antipsychotic Agents
PubMed: 34625500
DOI: 10.1136/postgradmedj-2021-141118 -
Annals of Emergency Medicine Jun 2019
Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles
PubMed: 31133187
DOI: 10.1016/j.annemergmed.2019.01.012 -
Annals of Emergency Medicine Jun 2019
Topics: Emergency Service, Hospital; Haloperidol; Midazolam; Olanzapine; Piperazines; Thiazoles
PubMed: 31133186
DOI: 10.1016/j.annemergmed.2019.01.011 -
Anaesthesia Oct 2023Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to... (Randomized Controlled Trial)
Randomized Controlled Trial
Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to prevent nausea and vomiting in palliative care and to treat chemotherapy-induced nausea and vomiting. This study aimed to examine whether pre-operative olanzapine, as a prophylactic anti-emetic added to intra-operative dexamethasone, ondansetron and total intravenous anaesthesia, reduced the incidence of postoperative nausea or vomiting. We performed a multiply-blinded randomised controlled trial in patients aged 18-60 years with cancer at high risk of postoperative nausea or vomiting (three or four risk factors according to the Apfel criteria) plus a previous history of chemotherapy-induced nausea and vomiting. Patients were allocated at random to receive 10 mg olanzapine or placebo orally 1 h before surgery in addition to a two-drug regimen (dexamethasone and ondansetron) and propofol anaesthesia to prevent postoperative nausea or vomiting. The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; 47 in the olanzapine group and 49 in the control group completed the study. The baseline characteristics of the groups were similar. The incidence of postoperative nausea or vomiting in the first 24 h after surgery was lower in the olanzapine group (12/47, 26%) than in the control group (31/49, 63%) (p = 0.008, RR 0.40 (95%CI 0.21-0.79)). Adding pre-operative oral olanzapine to intra-operative dexamethasone and ondansetron was highly effective in reducing the risk of postoperative nausea or vomiting in the first 24 hours after surgery in patients with a previous history of chemotherapy-induced nausea and vomiting and at least three Apfel risk factors for postoperative nausea or vomiting.
Topics: Humans; Antiemetics; Postoperative Nausea and Vomiting; Olanzapine; Ondansetron; Dexamethasone; Antineoplastic Agents; Double-Blind Method
PubMed: 37449978
DOI: 10.1111/anae.16081 -
International Journal of Pharmaceutics Oct 2021Pharmaceutical cocrystals and salts are extensively researched in recent years due to their ability to tune the physicochemical properties of active pharmaceutical...
Pharmaceutical cocrystals and salts are extensively researched in recent years due to their ability to tune the physicochemical properties of active pharmaceutical ingredients (APIs). A model API, olanzapine, an atypical antipsychotic drug classified as Biopharmaceutical Classification System class II, is used in this study. Cocrystals and salts of olanzapine are discovered using solvent drop grinding and ball milling. Appropriate coformers were selected based on a combination of hydrogen-bond propensity (HBP) and hydrogen-bond coordination (HBC) calculations. Eight new multicomponent phases of olanzapine, including one cocrystal hydrate with phenol; four anhydrous salts with salicylic acid, terephthalic acid, anthranilic acid, 3-hydroxybenzoic acid, and 2-aminoterephthalic acid; one salt dihydrate with terephthalic acid; and one salt solvate with 3-hydroxybenzoic acid and acetonitrile, have been discovered and characterized by PXRD and DSC. One reported cocrystal (olanzapine-resorcinol) has also been considered for the dissolution test. All these newly formed solid phases followed the "ΔpK rule of 3". The crystal structures of cocrystal/salts were determined by single-crystal X-ray (sc-XRD) diffraction. With the collected single-crystal data, the crystal packings were found to be primarily stabilized via strong hydrogen bonds between carboxyl, phenolic hydroxyl of co-formers/salt-formers with the piperazine and diazepine nitrogen of olanzapine, which confirmed the predicted result from the HBP and HBC calculations. HPLC coupled with UV-vis detector was used in the solubility and dissolution test instead of UV-vis spectroscopy, to avoid the peak overlap between olanzapine and co-formers/salt-formers. A threefold increase in the solubility was observed in olanzapinium 3-hydroxybenzoate and olanzapinium anthranilate, and an almost fivefold increase in solubility of olanzapinium 2-aminoterephthalate.
Topics: Crystallization; Hydrogen Bonding; Olanzapine; Salts; Solubility
PubMed: 34481007
DOI: 10.1016/j.ijpharm.2021.121063 -
The Primary Care Companion For CNS... Feb 2021
Topics: Aggression; Antipsychotic Agents; Benzodiazepines; Humans; Olanzapine
PubMed: 34000138
DOI: 10.4088/PCC.20l02719