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pharmacokinetics, antidepressant

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https://www.readbyqxmd.com/read/29230490/pharmacokinetic-study-of-tianeptine-and-its-active-metabolite-mc5-in-rats-following-different-routes-of-administration-using-a-novel-liquid-chromatography-tandem-mass-spectrometry-analytical-method
#1
Małgorzata Szafarz, Agnieszka Wencel, Krzysztof Pociecha, Filip A Fedak, Piotr Wlaź, Elżbieta Wyska
Tianeptine is an atypical antidepressant with a unique mechanism of action and recently it has been also reported that its major metabolite, compound MC5, possesses pharmacological activity similar to that of the parent drug. The current study aims to investigate the pharmacokinetics (PK) of both tianeptine and MC5 after intravenous or intraperitoneal administration of the parent drug as well as the metabolic ratio of MC5 in rats. To achieve these goals an LC-MS/MS method using the small sample volume for the quantitation of tianeptine and its active metabolite MC5 in rat plasma and liver perfusate has been developed and validated...
December 12, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29205993/should-patients-with-schizophrenia-receive-antidepressants
#2
Viacheslav Terevnikov, Jan-Henry Stenberg, Grigori Joffe
Antipsychotics play a key role in the pharmacological treatment of schizophrenia, and monotherapy is effective for most patients. Achieving an optimal treatment response is, however, often difficult. Combining an antidepressant drug to the antipsychotic regimen could potentially improve treatment outcomes, although the evidence supporting the use of such combinations is limited and contradictory. Positive evidence has mostly been obtained from the efficacy of antidepressants acting on monoamine receptors on the negative symptoms of schizophrenia...
2017: Duodecim; Lääketieteellinen Aikakauskirja
https://www.readbyqxmd.com/read/29189941/vortioxetine-clinical-pharmacokinetics-and-drug-interactions
#3
REVIEW
Grace Chen, Astrid-Maria Højer, Johan Areberg, George Nomikos
Vortioxetine is a novel antidepressant with multimodal activity currently approved for the treatment of major depressive disorder. Vortioxetine is orally administered once daily at 5- to 20-mg doses. The pharmacokinetics of vortioxetine are linear and dose proportional, with a mean terminal half-life of approximately 66 h and steady-state plasma concentrations generally achieved within 2 weeks of dosing. The mean absolute oral bioavailability of vortioxetine is 75%. No food effect on pharmacokinetics was observed...
November 30, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29156365/antidepressant-polypharmacy-and-the-potential-of-pharmacokinetic-interactions-doxepin-but-not-mirtazapine-causes-clinically-relevant-changes-in-venlafaxine-metabolism
#4
Michael Paulzen, Ekkehard Haen, Christoph Hiemke, Bianca Fay, Sandra Unholzer, Gerhard Gründer, Georgios Schoretsanitis
BACKGROUND: To uncover pharmacokinetic interactions between venlafaxine and doxepin or mirtazapine in a naturalistic sample. METHODS: A therapeutic drug monitoring database containing plasma concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. We included 1067 of 1594 patients in the analysis. Three study groups were considered; a group of patients under venlafaxine without confounding medications, V0 (n = 905), a group of patients co-medicated with doxepin, VDOX (n = 25) and a second group, co-medicated with mirtazapine, VMIR, n = 137...
November 13, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/29138563/squarticles-as-the-nanoantidotes-to-sequester-the-overdosed-antidepressant-for-detoxification
#5
Chun-Han Chen, Tse-Hung Huang, Ahmed O Elzoghby, Pei-Wen Wang, Chia-Wen Chang, Jia-You Fang
The increasing death rate caused by drug overdose points to an urgent demand for the development of novel detoxification therapy. In an attempt to detoxify tricyclic antidepressant overdose, we prepared a lipid nanoemulsion, called squarticles, as the nanoantidote. Squalene was the major lipid matrix of the squarticles. Here, we present the animal study to investigate both the pharmacokinetic and pharmacodynamic effects of squarticles on amitriptyline intoxication. The anionic and cationic squarticles had average diameters of 97 and 122 nm, respectively...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29135584/concomitant-medication-polypharmacy-interactions-and-imperfect-adherence-are-common-in-australian-adults-on-suppressive-art
#6
Krista J Siefried, Limin Mao, Lucette A Cysique, John Rule, Michelle L Giles, Don E Smith, James Mcmahon, Tim R Read, Catriona Ooi, Ban K Tee, Mark Bloch, John de Wit, Andrew Carr
OBJECTIVES: We quantified concomitant medication (CM) polypharmacy, pharmacokinetic (PK) and pharmacodynamic (PD) interactions, adverse effects and adherence in Australian adults on effective ART. DESIGN: Cross-sectional. METHODS: Patients recruited into a nation-wide cohort and assessed for prevalence and type of CM (including polypharmacy, defined as ≥5 CMs), PK or PD interactions, potential CM adverse effects and CM adherence. Factors associated with CM polypharmacy and with imperfect adherence were identified using multivariable logistic regression...
November 10, 2017: AIDS
https://www.readbyqxmd.com/read/29134501/pharmacokinetic-properties-of-saffron-and-its-active-components
#7
Azar Hosseini, Bibi Marjan Razavi, Hossein Hosseinzadeh
Saffron as a medicinal plant has many therapeutic effects. Phytochemical studies have reported that saffron is composed of at least four active ingredients which include crocin, crocetin, picrocrocin and safranal. The carotenoids of saffron are sensitive to oxygen, light, heat and enzymatic oxidization. However, regulation of these factors is required for saffron quality. Some pharmacologic effects of saffron and its active compounds include cardioprotective, neuroprotective, memory enhancer, antidepressant and anxiolytic...
November 13, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29126076/a-rapid-and-sensitive-chiral-lc-ms-ms-method-for-the-determination-of-ketamine-and-norketamine-in-mouse-plasma-brain-and-cerebrospinal-fluid-applicable-to-the-stereoselective-pharmacokinetic-study-of-ketamine
#8
Hidetoh Toki, Takuya Ichikawa, Akiko Mizuno-Yasuhira, Jun-Ichi Yamaguchi
A novel method for the rapid and sensitive chiral determination of ketamine and norketamine in mouse plasma, brain and cerebrospinal fluid (CSF) was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This method reduces the required matrix volume, compared with a previously reported chiral assay method for ketamine and norketamine. The method involves the deproteinization of a small amount of biological matrix (corresponding to 5μL of plasma, 10mg of brain, or 2.5μL of CSF) using a water-miscible organic solvent containing (2)H4-norketamine as an internal standard, the direct injection of the organic supernatant into an LC-MS/MS system, chiral separation on a CHIRALPAK AS-3R column (4...
October 7, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29125702/single-dose-pharmacokinetics-of-oral-cannabidiol-following-administration-of-ptl101-a-new-formulation-based-on-gelatin-matrix-pellets-technology
#9
Jacob Atsmon, Daphna Heffetz, Lisa Deutsch, Frederic Deutsch, Hagit Sacks
Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design...
November 10, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/29123929/palpitations-and-asthenia-associated-with-venlafaxine-in-a-cyp2d6-poor-metabolizer-and-cyp2c19-intermediate-metabolizer
#10
Sofia Garcia, Michael Schuh, Anvir Cheema, Herjot Atwal, Paldeep S Atwal
Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia...
2017: Case Reports in Genetics
https://www.readbyqxmd.com/read/29115994/exploring-venlafaxine-pharmacokinetic-variability-with-a-phenotyping-approach-a-multicentric-french-swiss-study-marvel-study
#11
Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, Philippe Courtet, Florence Galtier, Raphaëlle-Marie Richieri, Sophie Morange, Pierre-Michel Llorca, Wissam El-Hage, Thomas Desmidt, Frédéric Haesebaert, Philippe Vignaud, Jerôme Holtzmann, Jean-Luc Cracowski, Marion Leboyer, Antoine Yrondi, Fabienne Calvas, Liova Yon, Philippe Le Corvoisier, Olivier Doumy, Kyle Heron, Damien Montange, Siamak Davani, Julien Déglon, Marie Besson, Jules Desmeules, Emmanuel Haffen, Frank Bellivier
BACKGROUND: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis...
November 7, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29079874/study-on-the-effect-of-emd386088-a-5-ht6-receptor-partial-agonist-in-enhancing-the-anti-immobility-action-of-some-antidepressants-in-rats
#12
Magdalena Jastrzębska-Więsek, Agata Siwek, Anna Partyka, Marcin Kołaczkowski, Maria Walczak, Magdalena Smolik, Gniewomir Latacz, Katarzyna Kieć-Kononowicz, Anna Wesołowska
The effect of some antidepressants co-administered with EMD386088 in the modified forced swim test in rats was investigated. Additionally, the pharmacokinetics, metabolic stability, and the effect of EMD386088 on P450 cytochromes were determined. Intraperitoneal (i.p.) coadministration of EMD386088 (2.5 mg/kg) and imipramine (15 mg/kg), reboxetine (5 mg/kg), moclobemide (10 mg/kg), or bupropion (10 mg/kg) evoked significant antidepressant-like activity, whereas no effect was observed after joint administration of EMD386088 with s-citalopram (10 mg/kg)...
October 27, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/29046178/a-psychiatric-formulary-for-long-duration-spaceflight
#13
Eric Friedman, Brian Bui
Behavioral health is essential for the safety, well-being, and performance of crewmembers in both human spaceflight and Antarctic exploration. Over the past five decades, psychiatric issues have been documented in orbital spaceflight. In Antarctica, literature suggests up to 5% of wintering crewmembers could meet criteria for a psychiatric illness, including mood disorders, stressor-related disorders, sleep-wake disorders, and substance-related disorders. Experience from these settings indicates that psychiatric disorders on deep space missions must be anticipated...
November 1, 2017: Aerospace Medicine and Human Performance
https://www.readbyqxmd.com/read/29025271/psychotropic-drugs-and-cyp2d6-in-late-life-psychiatric-and-neurological-disorders-what-do-we-know
#14
Davide Seripa, Madia Lozupone, Eleonora Stella, Giulia Paroni, Paola Bisceglia, Maddalena La Montagna, Grazia D'onofrio, Carolina Gravina, Maria Urbano, Maria Giovanna Priore, Angela Lamanna, Antonio Daniele, Antonello Bellomo, Giancarlo Logroscino, Antonio Greco, Francesco Panza
Late-life psychiatric and neurological disorders (LLPND) are interesting models to understand the potential role of pharmacogenetics in drug management, since several pharmacological approaches for treating LLPND have proven to be ineffective or deleterious, thus resulting in therapeutic failures (TF) and adverse drug reactions (ADR). Common variants in the genes encoding the cytochrome P450 (CYP) enzyme system, the 'engine room' of drug metabolism, together with well-known age-related increased polypharmacy also contributed to the prevalence of TF and ADR observed in these patients, also rising number and time of hospital readmissions and rate of institutionalizations...
December 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28951668/development-and-evaluation-of%C3%A2-desvenlafaxine-loaded-plga-chitosan-nanoparticles-for-brain-delivery
#15
Gui-Feng Tong, Nan Qin, Li-Wei Sun
Depression is a debilitating psychiatric condition that remains the second most common cause of disability worldwide. Currently, depression affects more than 4 per cent of the world's population. Most of the drugs intended for clinical management of depression augment the availability of neurotransmitters at the synapse by inhibiting their neuronal reuptake. However, the therapeutic efficacy of antidepressants is often compromised as they are unable to reach brain by the conventional routes of administration...
September 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28951319/recent-advances-in-nanocarrier-loaded-gels-which-drug-delivery-technologies-against-which-diseases
#16
REVIEW
Marion Pitorre, Henri Gondé, Clotilde Haury, Marwa Messous, Jérémie Poilane, David Boudaud, Erdem Kanber, Glenn Alexis Rossemond Ndombina, Jean-Pierre Benoit, Guillaume Bastiat
The combination of pharmaceutical technologies can be a wise choice for developing innovative therapeutic strategies. The association of nanocarriers and gels provides new therapeutic possibilities due to the combined properties of the two technologies. Gels support the nanocarriers, localize their administration to the target tissue, and sustain their release. In addition to the properties afforded by the gel, nanocarriers can provide additional drug sustained release or different pharmacokinetic and biodistribution profiles than those from nanocarriers administered by the conventional route to improve the drug therapeutic index...
September 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28948135/pharmacological-management-of-anxiety-disorders-in-the-elderly
#17
Elizabeth A Crocco, Sindy Jaramillo, Caroline Cruz-Ortiz, Katherine Camfield
Anxiety disorders are common in the elderly. Additionally, anxiety symptoms often accompany co-morbid psychiatric, medical, as well as neurodegenerative diseases in the older population. Anxiety in the elderly, often accompanied by depression, can lead to worsening physical, cognitive and functional impairments in this vulnerable population. Antidepressants are considered first line treatment. Both SSRIs and SNRIs are efficacious and well-tolerated in the elderly. Some SSRIs are strong inhibitors of the cytochrome P450 hepatic pathway whereas others have less potential for drug interaction...
March 2017: Current Treatment Options in Psychiatry
https://www.readbyqxmd.com/read/28888484/prediction-of-human-efficacious-antidepressant-doses-using-the-mouse-forced-swim-test
#18
Eunice Yuen, Steven Swanson, Jeffrey M Witkin
The forced swim test (FST) is a commonly used preclinical animal behavioural model for prediction of antidepressant activity in humans. While the FST may qualitatively predict efficacy, less is known about the quantitative translation of FST data to human efficacious doses. Assessing quantitative translation allows better predictions of human efficacious doses and a higher chance of success in the drug development process. Dose-response and time-course FST experiments were carried out on mice using four marketed antidepressants (citalopram, desipramine, bupropion, desvenlafaxine) in addition to ketamine, all with varying mechanisms of action...
October 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28880242/synthesis-and-antidepressant-activity-profile-of-some-novel-benzothiazole-derivatives
#19
Ümide Demir Özkay, Ceren Kaya, Ulviye Acar Çevik, Özgür Devrim Can
Within the scope of our new antidepressant drug development efforts, in this study, we synthesized eight novel benzothiazole derivatives 3a-3h. The chemical structures of the synthesized compounds were elucidated by spectroscopic methods. Test compounds were administered orally at a dose of 40 mg/kg to mice 24, 5 and 1 h before performing tail suspension, modified forced swimming, and activity cage tests. The obtained results showed that compounds 3c, 3d, 3f-3h reduced the immobility time of mice as assessed in the tail suspension test...
September 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28876959/chirality-and-neuropsychiatric-drugs-an-update-on-stereoselective-disposition-and-clinical-pharmacokinetics-of-bupropion
#20
Ranjeet Prasad Dash, Rana Rais, Nuggehally R Srinivas
1. Bupropion, an antidepressant drug has been approved as a racemate containing equal amounts of R- and S-enantiomers. Recently, the chirality of bupropion has received significant attention in the delineation of stereoselective pharmacokinetic (PK) and disposition data. Although the non-stereoselective metabolism of bupropion was well established, the emerging data suggest that bupropion exhibits complex stereoselective metabolism, leading to the formation of various stereoisomeric metabolites. Along with the chiral PKs of bupropion, hydroxybupropion, threohydrobupropion and erythrohydrobupropion, the metabolism data also provided insights into the roles of both CYP2B6 and CYP2C19 enzymes in the stereoselective disposition...
October 13, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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