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Molecular Pharmaceutics Dec 2011Duloxetine hydrochloride (1) is an important antidepressant that acts as a serotonin and noradrenaline reuptake inhibitor that has only recently been characterized by...
Duloxetine hydrochloride (1) is an important antidepressant that acts as a serotonin and noradrenaline reuptake inhibitor that has only recently been characterized by single-crystal X-ray diffraction. This study describes an investigation into polymorphism of duloxetine hydrochloride, discusses the challenges of characterizing new structures, and reports a new metastable solvate (1(acetone)) where acetone is trapped in a duloxetine hydrochloride host lattice. In view of the importance of formulation processing and bioavailability characteristics of the crystalline forms of 1, a comprehensive structural study of 1(acetone) was carried out using single-crystal and powder X-ray diffraction, infrared and Raman spectroscopies, and solid-state NMR spectroscopy. The rapid desolvation from 1(acetone) to the stable unsolvated form was investigated, and the structures of free and solvated forms are discussed in terms of the noncovalent intermolecular interactions.
Topics: Acetone; Antidepressive Agents; Duloxetine Hydrochloride; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Solvents; Thiophenes; X-Ray Diffraction
PubMed: 22050389
DOI: 10.1021/mp200455u -
Prostaglandins & Other Lipid Mediators Dec 2020Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is currently recommended as a useful medicine to chronic pain including low back pain. However, as the analogy...
Duloxetine, a serotonin-norepinephrine reuptake inhibitor, is currently recommended as a useful medicine to chronic pain including low back pain. However, as the analogy of classical selective serotonin reuptake inhibitors, there is a concern to deteriorate osteoporosis with remaining to clarify the exact mechanism of duloxetine in bone metabolism. We have previously reported that prostaglandin E (PGE) induces the synthesis of both osteoprotegerin (OPG) and interleukin-6 (IL-6), essential regulators of bone metabolism, in osteoblast-like MC3T3-E1 cells. Based upon them, we herein investigated the mechanism whereby the effect of duloxetine on the synthesis of OPG and IL-6 induced by PGE in these cells. Duloxetine enhanced the release from MC3T3-E1 cells of both OPG and IL-6 stimulated by PGE. However, reboxetine, a selective and specific inhibitor of norepinephrine reuptake, failed to affect the PGE-induced release of OPG or IL-6. Oppositely, fluvoxamine and sertraline, agents belonging to the class of selective serotonin reuptake inhibitor, upregulated the PGE-stimulated release of both OPG and IL-6. Duloxetine amplified the expression of OPG mRNA and IL-6 mRNA stimulated by PGE. Duloxetine strengthened the PGE-induced p38 MAP kinase phosphorylation, which was amplified by fluvoxamine as well. SB203880, an inhibitor of p38 MAP kinase, suppressed the amplifying effects by duloxetine or fluvoxamine on the PGE-stimulated release of OPG and IL-6. These results strongly suggest that duloxetine could strengthen osteoblast activation by PGE through the upregulation of p38 MAP kinase, leading to increasing the synthesis of OPG and IL-6.
Topics: 3T3 Cells; Alprostadil; Animals; Drug Interactions; Duloxetine Hydrochloride; Mice; Osteoblasts; Phosphorylation; Resveratrol; Transcriptional Activation; Up-Regulation; p38 Mitogen-Activated Protein Kinases
PubMed: 33002595
DOI: 10.1016/j.prostaglandins.2020.106481 -
AAPS PharmSciTech Aug 2015This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation....
This study investigated the potential use of mesoporous silica nanoparticles (MSNs) as a carrier for duloxetine hydrochloride (DX), which is prone to acid degradation. Sol-gel and solvothermal methods were used to synthesize the MSNs, which, after calcination and drug loading, were then characterized using X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) technique, thermogravimetric analysis (TGA), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and diffuse reflectance ultraviolet-visible (DRS-UV-Vis) spectroscopy. Releases of DX from the MSNs were good in pH 7.4 (90%) phosphate buffer but poor in acidic pH (40%). In a comparative release study between the MSNs in phosphate buffer, TW60-3DX showed sustained release for 140 h, which was higher than the other nanoparticles. The mechanism of DX release from the MSNs was studied using Peppas kinetics model. The "n" value of all three MSNs ranged from 0.45 to 1 with a correlation coefficient (r (2)) >0.9, which indicated that the release of the drug from the system follows the anomalous transport or non-Fickian diffusion. The results supported the efficacy of mesoporous silica nanoparticles synthesized here as a promising carrier for duloxetine hydrochloride with higher drug loading and greater pH-sensitive release.
Topics: Calorimetry, Differential Scanning; Duloxetine Hydrochloride; In Vitro Techniques; Microscopy, Electron, Scanning; Nanoparticles; Silicon Dioxide; Spectrum Analysis; Thermogravimetry; X-Ray Diffraction
PubMed: 25604699
DOI: 10.1208/s12249-014-0273-x -
Basic & Clinical Pharmacology &... Jan 2016Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective... (Review)
Review
Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For the newer antidepressant group of serotonin and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data for duloxetine are significantly smaller but does not suggest a clinically important increased risk.
Topics: Abnormalities, Drug-Induced; Cohort Studies; Depressive Disorder, Major; Duloxetine Hydrochloride; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Exposure Delayed Effects; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 26435496
DOI: 10.1111/bcpt.12497 -
Clinical Neuropharmacology 2020
Topics: Duloxetine Hydrochloride; Olfaction Disorders; Selective Serotonin Reuptake Inhibitors
PubMed: 32106138
DOI: 10.1097/WNF.0000000000000381 -
The Journal of Arthroplasty Jun 2022Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Duloxetine, a serotonin-norepinephrine dual reuptake inhibitor, may improve analgesia after total knee arthroplasty (TKA). Previous studies had one primary outcome, did not consistently use multimodal analgesia, and used patient-controlled analgesia devices, potentially delaying discharge. We investigated whether duloxetine would reduce opioid consumption or pain with ambulation.
METHODS
A total of 160 patients received 60 mg duloxetine or placebo daily, starting from the day of surgery and continuing 14 days postoperatively. Patients received neuraxial anesthesia, peripheral nerve blocks, acetaminophen, nonsteroidal anti-inflammatory drugs, and oral opioids as needed. The dual primary outcomes were Numeric Rating Scale (NRS) scores with movement on postoperative days 1, 2, and 14, and cumulative opioid consumption surgery through postoperative day 14.
RESULTS
Duloxetine was noninferior to placebo for both primary outcomes and was superior to placebo for opioid consumption. Opioid consumption (mean ± SD) was 288 ± 226 mg OME [94, 385] vs 432 ± 374 [210, 540] (duloxetine vs placebo) P = .0039. Pain scores on POD14 were 4.2 ± 2.0 vs 4.8 ± 2.2 (duloxetine vs placebo) P = .018. Median satisfaction with pain management was 10 (8, 10) and 8 (7, 10) (duloxetine vs placebo) P = .046. Duloxetine reduced interference by pain with walking, normal work, and sleep.
CONCLUSION
The 29% reduction in opioid use corresponds to 17 fewer pills of oxycodone, 5 mg, and was achieved without increasing pain scores. Considering the ongoing opioid epidemic, duloxetine can be used to reduce opioid usage after knee arthroplasty in selected patients that can be appropriately monitored for potential side effects of the medication.
Topics: Analgesia, Patient-Controlled; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Double-Blind Method; Duloxetine Hydrochloride; Humans; Opioid-Related Disorders; Pain, Postoperative
PubMed: 35346549
DOI: 10.1016/j.arth.2022.02.022 -
Zeitschrift Fur Rheumatologie May 2019Peripheral neuropathies are probably an under-diagnosed complication of many rheumatic diseases. In some cases they take a mild clinical course, in others they cause... (Review)
Review
Peripheral neuropathies are probably an under-diagnosed complication of many rheumatic diseases. In some cases they take a mild clinical course, in others they cause severe impairment of patients' quality of life. A precise diagnosis and etiological classification are of major importance for successful treatment and prognosis of peripheral neuropathies. A detailed patient history and physical examination are the foundation of every diagnostic approach. Electrophysiological studies are obligatory when peripheral neuropathy is suspected, whereas nerve or nerve-muscle biopsies are indicated only in selected cases. Therapeutic approaches are often complicated by a lack of evidence. They correspond to frequently tested immunosuppressive treatment of the underlying disease, such as glucocorticoids, cyclophosphamide, mycophenolate mofetil and intravenous immunoglobulins and are based on the symptomatic pain treatment of other neuropathies. As first-line treatment gabapentin, pregabalin, duloxetine, venlafaxine and tricyclic antidepressants are frequently used.
Topics: Duloxetine Hydrochloride; Humans; Pain Management; Peripheral Nervous System Diseases; Quality of Life; Rheumatic Diseases
PubMed: 30944998
DOI: 10.1007/s00393-019-0621-z -
Systematic Reviews Apr 2022Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly...
Tolerability of duloxetine in elderly and in non-elderly adults: a protocol of a systematic review and individual participant data meta-analysis of randomized placebo-controlled trials.
BACKGROUND
Duloxetine is an antidepressant that benefits from a wide range of approval in the elderly population, while its safety for use compared to non-elderly is not clearly assessed. This protocol outlines a systematic review and individual participant data meta-analysis comparing the tolerability of duloxetine between elderly and non-elderly.
METHODS
Searches will be conducted in PubMed, ClinicalTrials.gov , Clinicaltrialsregister.eu, data sharing platforms, FDA drug approval packages, European public assessment reports and withdrawn applications from the EMA website. The review will be performed on studies available in electronic databases from their date of inception to the 31 March 2022. Only randomized controlled clinical trials, comparing duloxetine to placebo, will be included in this meta-analysis. The studies will be selected if they comprise both elderly and non-elderly adults, in conditions of use of duloxetine approved by the European Medical Agency (EMA) and the Food and Drug Administration (FDA). The primary outcome will be the rate ratio of serious adverse events under duloxetine compared to placebo, between participants at least 65 years old and non-elderly. Second, the number of any adverse events, clinical efficacy and quality of life will be compared between elderly and non-elderly under both interventions. The quality of evidence in the tolerability of duloxetine will be assessed using the GRADE system. A one or two-stage individual participant data random effect meta-analysis will be conducted depending on the availability of the data.
DISCUSSION
This meta-analysis will investigate the tolerability safety of duloxetine in the elderly population across all conditions approved by European and American regulatory authorities. The results from this meta-analysis are intended to help prescribers to provide better care for the elderly population.
SYSTEMATIC REVIEW REGISTRATION
The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD42019130488 ).
Topics: Adult; Aged; Antidepressive Agents; Duloxetine Hydrochloride; Humans; Meta-Analysis as Topic; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Treatment Outcome
PubMed: 35428340
DOI: 10.1186/s13643-022-01945-0 -
Clinical NeuropharmacologyIn persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing... (Review)
Review
In persons with narcolepsy type 1, sudden withdrawal of antidepressants can cause status cataplecticus. We describe a 77-year-old female patient with long-standing history of narcolepsy type 1 complaining of recurrent short sudden episodes of whole-body paralysis, with preserved consciousness and memory. Episodes started an hour after her family invited her to celebrate Mother's Day. One week prior, patient had abruptly discontinued duloxetine. Cataplectic episodes resolved within 24 hours after resumption of duloxetine and treatment of hypokalemia. Status cataplecticus has been reported after withdrawal of venlafaxine, fluoxetine, and clomipramine. This is the first report of status cataplecticus due to duloxetine withdrawal. We review the pathophysiology of antidepressant withdrawal-induced status cataplecticus. In persons with narcolepsy type 1, physicians discontinuing any antidepressant should counsel on adverse effects of antidepressant withdrawal and reduce the dose in tapering manner.
Topics: Female; Humans; Aged; Duloxetine Hydrochloride; Cataplexy; Narcolepsy; Antidepressive Agents; Venlafaxine Hydrochloride
PubMed: 37748003
DOI: 10.1097/WNF.0000000000000563 -
Journal of Pharmaceutical and... Mar 2010A stability-indicating gradient reverse phase liquid chromatographic purity and assay method for duloxetine hydrochloride (DUH) was developed and validated. DUH was...
A stability-indicating gradient reverse phase liquid chromatographic purity and assay method for duloxetine hydrochloride (DUH) was developed and validated. DUH was subjected to the stress conditions and it is sensitive towards oxidative, acid and hydrolytic degradation. Successful separation of DUH from its two process impurities and one degradation impurity formed under stress conditions was achieved on a Symmetry C18, 250x4.6mm, 5microm column using a gradient mixture of solvent A (0.01M potassium dihydrogen orthophosphate having 0.2% triethyl amine, pH adjusted to 2.5 with orthophosphoric acid) and solvent B (20:80 v/v mixture of acetonitrile and methanol). The flow rate is 1ml/min and the detection wavelength is 230nm. The mass balance was found to be in the range of 99.2-99.7% in all the stressed conditions.
Topics: Antidepressive Agents; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Drug Contamination; Drug Stability; Duloxetine Hydrochloride; Hydrogen-Ion Concentration; Hydrolysis; Oxidation-Reduction; Reproducibility of Results; Technology, Pharmaceutical; Thiophenes
PubMed: 20005658
DOI: 10.1016/j.jpba.2009.10.025