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Spectrochimica Acta. Part A, Molecular... Dec 2008The fluorescence characteristics of duloxetine hydrochloride are studied in this paper. The fluorescence emission spectra of duloxetine demonstrate that intramolecular...
The fluorescence characteristics of duloxetine hydrochloride are studied in this paper. The fluorescence emission spectra of duloxetine demonstrate that intramolecular charge-transfer takes place between thiophene ring and napthalenyloxy group upon irradiation. The effects of excitation light, solvent system, variation of solution pH value, metal ions and vitamin C on the fluorescence spectra of duloxetine hydrochloride are elucidated, respectively. A spectrofluorometric method of quantitative determination of duloxetine in dosage form is reported for the first time, the linear range is 7.14 x 10(-8)mol/L to 1.43 x 10(-5)mol/L, the linear correlation coefficient r is equal to 0.9997, and the detection limit is 3.5 x 10(-8)mol/L. The accuracy and the precision are satisfactory.
Topics: Antidepressive Agents; Ascorbic Acid; Cations; Duloxetine Hydrochloride; Hydrogen-Ion Concentration; Metals; Molecular Structure; Photochemical Processes; Solvents; Spectrometry, Fluorescence; Temperature; Thiophenes
PubMed: 18374628
DOI: 10.1016/j.saa.2008.02.017 -
Journal of Clinical Anesthesia Nov 2022To test the hypothesis that duloxetine reduces postoperative morphine consumption and pain intensity in patients undergoing major colonic surgeries. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVE
To test the hypothesis that duloxetine reduces postoperative morphine consumption and pain intensity in patients undergoing major colonic surgeries.
DESIGN
Single-center, prospective, double-blinded, randomized, controlled trial.
SETTING
Tertiary university hospital, from December 2019 to September 2021.
PATIENTS
Sixty 18-85 years old, ASA I - III patients undergoing elective open major colonic surgeries were randomly allocated into duloxetine (duloxetine) or placebo (placebo) groups (n = 30 per group).
INTERVENTIONS
Duloxetine 60 mg or placebo was administered orally 2 h before and 24 h after surgery.
MEASUREMENTS
PCA morphine consumption, surgical pain at rest, and movement measured on 10-cm visual analog scales (VAS), Ramsay sedation scores, and the incidence of adverse effects potentially associated with duloxetine were assessed at patients' admission to the post-anesthesia care unit (PACU), 6, 24, and 48 h postoperatively (PO).
MAIN RESULTS
After adjusting for age, BMI, ASA physical status, education level, and incision type, no differences were found between groups in PCA morphine consumption 24 PO h (duloxetine = 5.44 ± 2.06 mg; placebo = 10.33 ± 2.06 mg, p = 0.62) or 48 h PO (duloxetine = 9.18 ± 2.06 mg, placebo = 12.93 ± 2.06, p = 1). Pain at rest also did not differ between groups at 24 h PO (duloxetine = 1.76 ± 0.67 cm; placebo = 1 ± 0.67 cm, p = 1) or at 48 h PO (duloxetine = 0.84 ± 0.67 cm; placebo = 0.49 ± 0.67 cm, p = 1). Similarly, groups did not differ regarding pain on movement at 24 h PO (duloxetine = 2.09 ± 0.68 cm; placebo = 1.80 ± 0.68, p = 1) or at 48 h PO (duloxetine = 1.16 ± 0.68 cm; placebo = 0.88 ± 0.68 cm, p = 1). Sedation scores and adverse effects also did not differ between groups.
CONCLUSION
Under this study's conditions, short-term duloxetine did not reduce total opioid consumption or pain intensity during the initial 48 h following major colon surgery.
Topics: Analgesics, Opioid; Colectomy; Double-Blind Method; Duloxetine Hydrochloride; Humans; Morphine; Pain, Postoperative; Prospective Studies
PubMed: 35963028
DOI: 10.1016/j.jclinane.2022.110948 -
Journal of Chromatographic Science Nov 2010A reproducible gradient reversed-phase ultra-performance liquid chromatographic method is developed for quantitative determination of duloxetine hydrochloride in...
A reproducible gradient reversed-phase ultra-performance liquid chromatographic method is developed for quantitative determination of duloxetine hydrochloride in pharmaceutical dosage forms. The method is also applicable for analysis of related substances and for study of in vitro dissolution profiles. Chromatographic separation is achieved on a 50 mm × 4.6 mm, 1.8 μm C-18 column. Mobile phase A contains a mixture of 0.01 M KH(2)PO(4) (pH 4.0) buffer, tetrahydro furan, and methanol in the ratio 67:23:10 (v/v/v), respectively, and mobile phase B contains a mixture of 0.01 M KH(2)PO(4), (pH 4.0) buffer, and acetonitrile in the ratio 60:40 (v/v), respectively. The flow rate is 0.6 mL/min, and the detection wavelength is monitored at 236 nm. Resolution of duloxetine hydrochloride and three potential impurities is greater than 2.0 for all pairs of components. The drug was subjected to ICH prescribed hydrolytic, oxidative, photolytic, and thermal stress conditions. Method is validated for linearity, specificity, accuracy, precision, ruggedness, and robustness.
Topics: Chromatography, High Pressure Liquid; Dosage Forms; Drug Stability; Duloxetine Hydrochloride; Solubility; Thiophenes
PubMed: 21044412
DOI: 10.1093/chromsci/48.10.819 -
European Journal of Pain (London,... Sep 2022Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these... (Randomized Controlled Trial)
Randomized Controlled Trial
The effect of duloxetine on mechanistic pain profiles, cognitive factors and clinical pain in patients with painful knee osteoarthritis-A randomized, double-blind, placebo-controlled, crossover study.
BACKGROUND
Duloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof-of-mechanism, randomized, placebo-controlled, crossover, double-blinded trial evaluated the effect of duloxetine on quantitative sensory testing (QST), cognitive factors and clinical pain in patients with osteoarthritis and to predict the analgesic effect.
METHODS
Twenty-five patients completed this cross-over study with either 18-week duloxetine (maximum 60 mg/daily) followed by placebo or vice-versa. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation were assessed using cuff algometry. The Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale evaluated cognitive factors. Clinical pain was assessed using Brief Pain Inventory and Western Ontario and McMaster Universities Osteoarthritis Index. Linear regression models were used to predict the analgesic effect of duloxetine.
RESULTS
Depending on the clinical pain outcome, 40%-68% of patients were classified as responders to duloxetine. Linear regression models predicted the analgesic effect (predictive value of 45%-75% depending on clinical pain outcome parameter) using a combination of pretreatment QST parameters, cognitive factors and clinical pain. No significant changes were found for QST, cognitive factors or clinical pain on a group level when comparing duloxetine to placebo.
CONCLUSION
A combination of pretreatment QST, cognitive factors and clinical pain was able to predict the analgesic response of duloxetine. However, in this relatively small study, duloxetine did not selectively modulate QST, cognitive factors or clinical pain intensity when compared with placebo.
SIGNIFICANCE
Duloxetine is proposed as a treatment for chronic pain. Pre-clinical trials suggest that duloxetine provides analgesia through modulation of descending pain inhibitory pathways or through improvements in cognitive factors. The current study demonstrates that pretreatment mechanistic pain profiling, cognitive factors and clinical pain can predict the analgesic effect of duloxetine and that only a subset of patients might benefit from duloxetine treatment.
Topics: Analgesics; Chronic Pain; Cognition; Cross-Over Studies; Double-Blind Method; Duloxetine Hydrochloride; Humans; Osteoarthritis, Knee; Treatment Outcome
PubMed: 35638317
DOI: 10.1002/ejp.1988 -
Journal of Separation Science Aug 2022Two anionic β-cyclodextrins as chiral selectors were successfully applied in the enantioseparation of N-methyl duloxetine, duloxetine, and fluoxetine by countercurrent...
Two anionic β-cyclodextrins as chiral selectors were successfully applied in the enantioseparation of N-methyl duloxetine, duloxetine, and fluoxetine by countercurrent chromatography. Sulfobutyl ether-β-cyclodextrin and carboxymethyl-β-cyclodextrin showed opposite enantioselectivity for both duloxetine and N-methyl duloxetine enantiomers. Two biphasic solvent systems, n-hexane: 0.1 mol/L phosphate buffer pH 7.6 with 50 mmol/L of sulfobutyl ether-β-cyclodextrin (1:1, v/v) and n-hexane: 0.1 mol/L phosphate buffer pH 7.2 with 50 mmol/L of carboxymethyl-β-cyclodextrin (1:1, v/v), were selected for N-methyl duloxetine. Enantioseparation of duloxetine was achieved by recycling countercurrent chromatography using a solvent system composed of n-butyl acetate: 0.1 mol/L phosphate buffer pH 7.2 with 20 mmol/L of sulfobutyl ether-β-cyclodextrin or carboxymethyl-β-cyclodextrin (1:1, v/v). A solvent system composed of n-hexane: n-butyl acetate: 0.1 mol/L phosphate buffer pH 7.6 containing 20 mmol/L of sulfobutyl ether-β-cyclodextrin (6:4:10, v/v) was selected for enantioseparation of fluoxetine.
Topics: Anions; Countercurrent Distribution; Duloxetine Hydrochloride; Ethers; Fluoxetine; Phosphates; Solvents; Stereoisomerism; beta-Cyclodextrins
PubMed: 35598113
DOI: 10.1002/jssc.202200151 -
The Lancet. Oncology Jan 2017
Topics: Analgesics; Aromatase Inhibitors; Arthralgia; Breast Neoplasms; Duloxetine Hydrochloride; Female; Humans; Pain Measurement; Randomized Controlled Trials as Topic; Serotonin and Noradrenaline Reuptake Inhibitors; Time Factors; Treatment Outcome
PubMed: 27989429
DOI: 10.1016/S1470-2045(16)30656-8 -
Journal of the Neurological Sciences Jul 2020Duloxetine proved effective for treating pain in people with Parkinson's disease in a single-arm, open-label study. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Duloxetine proved effective for treating pain in people with Parkinson's disease in a single-arm, open-label study.
OBJECTIVE
To evaluate the efficacy of duloxetine in a double-blind, randomized, placebo-controlled trial.
METHODS
We randomly assigned 46 patients with Parkinson's disease with pain to either the duloxetine 40 mg/day arm or the placebo arm. After 10 weeks, we tested the change from baseline in 24-hour average pain severity measured by a visual analogue scale.
RESULTS
We could not confirm the effect of duloxetine on pain. Exploratory analyses indicated that treatment with duloxetine was associated with improved scores on the Unified Parkinson's Disease Rating Scale Part III and 3 domains of the Parkinson's Disease Questionnaire - 39.
CONCLUSIONS
The study failed to provide evidence for the use of duloxetine for treating pain in people with Parkinson's disease.
Topics: Dopamine Agents; Double-Blind Method; Duloxetine Hydrochloride; Humans; Pain; Parkinson Disease; Treatment Outcome
PubMed: 32299024
DOI: 10.1016/j.jns.2020.116833 -
Anesthesia and Analgesia Mar 2016Antidepressant S-duloxetine alleviates intractable pain associated with diabetic peripheral neuropathy and fibromyalgia. It also reduces both acute and persistent pain...
BACKGROUND
Antidepressant S-duloxetine alleviates intractable pain associated with diabetic peripheral neuropathy and fibromyalgia. It also reduces both acute and persistent pain in various animal models. This study addresses whether the enantiomer, R-duloxetine, and the homolog, N-methyl duloxetine, could act as analgesics and whether they block neuronal Na⁺ channels.
METHODS
The rat incision plus extension model on the dorsothoracic skin was applied to evoke postoperative mechanoallodynia and hyperalgesia, measured for 5 days postoperatively by local responses to von Frey filaments. R-Duloxetine and N-methyl duloxetine were administered systemically (intraperitoneal) or locally (subcutaneous [SC]) 1 hour before the surgery. The block of Na currents in rat neuronal GH3 cells was determined under the whole-cell configuration.
RESULTS
Ipsilateral SC injections (2 mg/0.4 mL) of R-duloxetine and N-methyl duloxetine reduced both postoperative allodynia and hyperalgesia by approximately 89% to 99% in the area under the curve of skin responses next to incision over 5 days. Systemic intraperitoneal injections at a higher dosage (10 mg) had smaller analgesic effects (reduced by approximately 53%-69%), whereas contralateral SC injections (10 mg) were ineffective. Both R-duloxetine and N-methyl duloxetine blocked neuronal Na⁺ currents, with a higher affinity for the inactivated than the resting states. In addition, both drugs elicited significant use-dependent block of Na currents when stimulated at 5 Hz.
CONCLUSIONS
R-Duloxetine and N-methyl duloxetine are highly effective against postoperative pain using the skin incision model, and they elicit both tonic and use-dependent block of neuronal Na⁺ channels. Our results suggest that R-duloxetine and N-methyl duloxetine are applicable as novel analgesics.
Topics: Analgesics; Animals; Antidepressive Agents, Second-Generation; Cell Line; Duloxetine Hydrochloride; Hyperalgesia; Injections, Intraperitoneal; Injections, Subcutaneous; Male; Neurons; Pain, Postoperative; Patch-Clamp Techniques; Physical Stimulation; Pituitary Gland; Rats; Rats, Sprague-Dawley; Sodium Channel Blockers
PubMed: 26646348
DOI: 10.1213/ANE.0000000000001086 -
Medical Oncology (Northwood, London,... Aug 2017Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately...
Duloxetine is an effective therapeutic agent for chemotherapy-induced peripheral neuropathy (CIPN). However, predictors of duloxetine response have not been adequately explored. Therefore, this retrospective study was performed to identify predictive factors of duloxetine response in CIPN patients to guide future strategies to improve the quality of life of patients undergoing chemotherapy. The participants were 74 cancer patients who were given duloxetine for relief of CIPN at our institute between October 2010 and January 2016. Variables were extracted from clinical records for regression analysis of factors related to relief of CIPN. We evaluated the effect of duloxetine 2 weeks after administration. Groups were categorized according to degree of improvement: poor, effective, and very effective. Multivariate ordered logistic regression analysis was performed to identify predictive factors for the usefulness of duloxetine. Threshold measures were examined using a receiver operating characteristic analysis (ROC) curve. Body height [odds ratio (OR) 0.943, 95% confidence interval (CI) 0.889-0.997; P = 0.0387], history of docetaxel use (OR 0.084, 95% Cl 0.009-0.814; P = 0.0325), and site of symptom (upper limb) (OR 3.848, 95% Cl 1.072-13.807; P = 0.0387) were significant factors related to the effect of duloxetine. ROC curve analysis of the poor effect group indicated a threshold for body height of >171.4 cm (area under the curve [AUC] = 0.61). In conclusion, body height (low), history of docetaxel use (less), and site of symptom (upper limb) were shown to be predictive factors for the usefulness of duloxetine for CIPN in patients undergoing chemotherapy.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Body Height; Docetaxel; Duloxetine Hydrochloride; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Quality of Life; ROC Curve; Retrospective Studies; Taxoids
PubMed: 28687964
DOI: 10.1007/s12032-017-0995-1 -
International Journal of Molecular... Dec 2017Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and...
Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α₁-adrenergic receptor antagonists, 10 μg); however, idazoxan (α₂-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α₁-adrenergic receptors.
Topics: Adrenergic alpha-2 Receptor Antagonists; Animals; Duloxetine Hydrochloride; Male; Mice; Mice, Inbred C57BL; Neuralgia; Neurons; Organoplatinum Compounds; Oxaliplatin; Rats; Rats, Sprague-Dawley; Spinal Cord
PubMed: 29206213
DOI: 10.3390/ijms18122626