-
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 Primary Care Companion For CNS... May 2022
Topics: Duloxetine Hydrochloride; Erythema Multiforme; Humans
PubMed: 35522835
DOI: 10.4088/PCC.21cr02983 -
Brain and Nerve = Shinkei Kenkyu No... Mar 2023Antinociceptive therapy for chronic neuropathic pain is anecdotal in nature based on a physician's preference. However, evidence-based therapy is expected, following the...
Antinociceptive therapy for chronic neuropathic pain is anecdotal in nature based on a physician's preference. However, evidence-based therapy is expected, following the chronic pain guideline established in 2021, supported by 10 pain-associated Japanese medical societies. The guideline strongly recommends the use of Ca-channel α2δ ligands (pregabalin, gabapentin, and mirogabalin) and duloxetine for pain relief. International guidelines also recommend administration of tricyclic antidepressants as first-line agents. Recent studies have described three classes of medicines that show comparable antinociceptive effects in painful diabetic neuropathy. Furthermore, a combination of first-line agents can improve efficacy. Antinociceptive medical therapy should be individualized based on the patient's condition and adverse effect profile of each medication.
Topics: Humans; Analgesics; Chronic Pain; Pregabalin; Gabapentin; Duloxetine Hydrochloride; Diabetic Neuropathies
PubMed: 36890758
DOI: 10.11477/mf.1416202312 -
Osteoarthritis and Cartilage Jan 2021Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States.
OBJECTIVE
Establish the impact of pain severity on the cost-effectiveness of generic duloxetine for knee osteoarthritis (OA) in the United States.
DESIGN
We used a validated computer simulation of knee OA to compare usual care (UC) - intra-articular injections, opioids, and total knee replacement (TKR) - to UC preceded by duloxetine in those no longer achieving pain relief from non-steroidal anti-inflammatory drugs (NSAIDs). Outcomes included quality-adjusted life years (QALYs), lifetime medical costs, and incremental cost-effectiveness ratios (ICERs). We considered cohorts with mean ages 57-75 years and Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain 25-55 (0-100, 100-worst). We derived inputs from published data. We discounted costs and benefits 3% annually. We conducted sensitivity analyses of duloxetine efficacy, duration of pain relief, toxicity, and costs.
RESULTS
Among younger subjects with severe pain (WOMAC pain = 55), duloxetine led to an additional 9.6 QALYs per 1,000 subjects (ICER = $88,500/QALY). The likelihood of duloxetine being cost-effective at willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY was 40% and 54%. Offering duloxetine to older patients with severe pain led to ICERs >$150,000/QALY. Offering duloxetine to subjects with moderate pain (pain = 25) led to ICERs <$50,000/QALY, regardless of age. Among knee OA subjects with severe pain (pain = 55) who are unwilling or unable to undergo TKR, ICERs were <$50,600/QALY, regardless of age.
CONCLUSIONS
Duloxetine is a cost-effective addition to knee OA UC for subjects with moderate pain or those with severe pain unable or unwilling to undergo TKR. Among younger subjects with severe pain, duloxetine is cost-effective at WTP thresholds >$88,500/QALY.
Topics: Aged; Analgesics; Analgesics, Opioid; Arthroplasty, Replacement, Knee; Computer Simulation; Cost-Benefit Analysis; Duloxetine Hydrochloride; Glucocorticoids; Humans; Injections, Intra-Articular; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Quality-Adjusted Life Years
PubMed: 33171315
DOI: 10.1016/j.joca.2020.10.001 -
The Clinical Journal of Pain Nov 2021We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We conducted the updated systematic review and meta-analysis of the best available quantitative and qualitative evidence to evaluate the effects and safety of duloxetine for the treatment of knee osteoarthritis (OA) pain.
METHODS
A comprehensive literature search used 3 English and 4 Chinese biomedical databases from inception through July 10, 2020. We included randomized controlled trials of duloxetine with intervention duration of 2 weeks or longer for knee OA. The primary outcome was pain intensity measured by Brief Pain Inventory and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcome measurements included 36-Item Short Form Health Survey, Patient's Global Impression of Improvement, Clinical Global Impressions of Severity, and adverse events (AEs). The quality of all included studies was evaluated using the Cochrane risk-of-bias criteria. The review was registered in the PROSPERO (CRD 42020194072).
RESULTS
Six studies totaling 2059 patients met the eligibility criteria. Duloxetine had significant reductions in Brief Pain Inventory 24 hours average pain (mean difference [MD]=-0.74; 95% confidence interval [CI], -0.92 to -0.57; P<0.00001; I2=13%; 5 trials; 1695 patients); patient general activity (MD=-0.76; 95% CI, -0.96 to -0.56; P<0.00001; I2=0%; 5 trials; 1694 patients) WOMAC physical function subscale (MD=-4.22; 95% CI, -5.14 to -3.30; P<0.00001; I2=26%; 5 trials; 1986 patients); Patient's Global Impression of Improvement (MD=-0.48; 95% CI, -0.58 to -0.37; P<0.00001; I2=29%; 5 trials; 1741 patients); and Clinical Global Impressions of Severity (MD=-0.34; 95% CI, -0.44 to -0.24; P<0.00001; I2=0%; 4 trials; 1178 patients) compared with placebo control. However, no difference on WOMAC pain subscale (standard mean difference=-1.68; 95% CI, -3.45 to 0.08; P=0.06; I2=100%; 3 trials; 1104 patients) and in serious AEs (risk ratio=0.92; 95% CI, 0.40-2.11; P=0.84; I2=0%; 5 trials; 1762 patients) between duloxetine and placebo. Furthermore, duloxetine failed to show superior effects for improving the life quality and demonstrated more treatment-emergent AEs.
CONCLUSION
Duloxetine may be an effective treatment option for knee OA patients but further rigorously designed and well-controlled randomized trials are warranted.
Topics: Duloxetine Hydrochloride; Humans; Knee Joint; Osteoarthritis, Knee; Pain; Pain Measurement
PubMed: 34483232
DOI: 10.1097/AJP.0000000000000975 -
Journal of Gynecology Obstetrics and... Mar 2022To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the efficacy and safety of preoperative duloxetine on postoperative pain management after gynecologic laparoscopic surgeries.
METHODS
A systematic search was done in Cochrane Library, PubMed, ISI web of science, and Scopus from inception to September 2021. We selected randomized clinical trials (RCTs) that compared preoperative duloxetine (intervention group) versus placebo (control group) among women undergoing gynecologic laparoscopic surgeries. Our primary outcomes were pain scores evaluated by the Visual Analog Scale (VAS) at 2, 6, 12, and 24 h postoperatively. Our secondary outcomes were the time required for the first analgesic request in minutes, postoperative analgesic consumption in milligrams, length of hospital stay in days, and side effects.
RESULTS
Four RCTs with a total number of 244 patients were included in our systematic review and meta-analysis. We found duloxetine was linked to a significant reduction in VAS pain scores at different time intervals. The first analgesic request was significantly earlier in the placebo group than in the duloxetine group (p = 0.03). In addition, duloxetine significantly reduced the postoperative analgesic consumption compared to placebo (MD= -41.97, 95% CI [-53.23, -30.72], p<0.001). However, both groups did not differ in the length of hospital stay and side effects.
CONCLUSIONS
Duloxetine administration prior to gynecological laparoscopic surgeries is safe and effective in improving postoperative pain and analgesia.
Topics: Duloxetine Hydrochloride; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Pain, Postoperative; Randomized Controlled Trials as Topic
PubMed: 34974147
DOI: 10.1016/j.jogoh.2021.102305 -
Drug Delivery Nov 2017Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral... (Comparative Study)
Comparative Study Randomized Controlled Trial
Duloxetine hydrochloride (DH) is a serotonin-norepinephrine reuptake inhibitor (SSNRI) indicated for the treatment of depression. Duloxetine suffers from reduced oral bioavailability (≈50%) due to hepatic metabolism. This study aims to develop DH buccoadhesive films to improve its bioavailability. DH buccoadhesive films were prepared adopting the solvent casting method using hydroxypropyl methylcellulose (HPMC) and polyvinyl alcohol (PVA). The prepared films were evaluated for weight uniformity, drug content, surface pH, swelling index, mucoadhesion strength and drug release percentages. Accelerated stability and bioavailability studies in healthy human volunteers were also performed for the selected films. Results of the evaluation tests showed that the optimum physicochemical characters were obtained by the films prepared with 2% HPMC using 10% propylene glycol (F2 films). Accelerated stability studies revealed that DH showed proved stability throughout the experiment time. DH bioavailability from F2 films was determined and compared with that of the marketed oral capsules (Cymbalta 30 mg). The pharmacokinetic results showed that C for F2 was higher than the market product. In addition, ANOVA analysis showed that a T of F2 film was significantly lower, while, the AUC of F2 was significantly higher than that of Cymbalta capsules. The percentage relative bioavailability of DH from F2 was found to be 296.39%. Therefore, the prepared buccal films offer an alternative route for the administration of DH with the possibility of improving its bioavailability.
Topics: Adhesiveness; Administration, Buccal; Animals; Biological Availability; Chemistry, Pharmaceutical; Chickens; Cross-Over Studies; Drug Delivery Systems; Drug Liberation; Duloxetine Hydrochloride; Humans; Hypromellose Derivatives; Mouth Mucosa; Polyvinyl Alcohol
PubMed: 29172829
DOI: 10.1080/10717544.2017.1402216 -
Pain Practice : the Official Journal of... Sep 2023Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral duloxetine, when given perioperatively, is any better than a placebo in managing postoperative pain. Effects of duloxetine on postoperative pain scores, time to first rescue analgesia, postoperative rescue analgesia consumption, side effects attributable to duloxetine, and patient satisfaction profile were assessed.
METHOD
MEDLINE, Web of Science, EMBASE, Scholar Google, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched with keywords including "Duloxetine" AND "postoperative pain", "Duloxetine" AND "acute pain" and with "Duloxetine" till October 2022. This meta-analysis included randomized clinical trials in which perioperative duloxetine 60 mg per oral was administered not more than 7 days before surgery and for at least 24 after surgery but not more than 14 days after surgery. All RCTs in which the comparator is placebo and outcomes related to analgesic efficacy like pain scores, opioid consumption, and side effects of duloxetine until 48 h postoperatively were included. Data were extracted from the studies and a risk of bias summary was formed using the Cochrane Collaboration tool. Effect sizes were given as standardized mean differences for continuous outcomes and risk ratios (RR) by the Mantel-Haenszel test for the categorical outcome. Confirmation of publication bias was done by Egger's regression test (p < 0.05). If publication bias or heterogeneity was detected, the trim-and-fill method was used to calculate the adjusted effect size. Sensitivity analysis was done by leaving one out method after excluding the study with a high risk of bias. Subgroup analysis was done based on the type of surgery and gender. The study was prospectively registered in the PROSPERO under the registration number CRD42019139559.
FINDINGS
29 studies with 2043 patients met the inclusion criteria and were reviewed for this meta-analysis. Postoperative pain scores at 24 h [Std. Mean Difference (95% CI); -0.69 (-1.07, -0.32)] and at 48 h [-1.13 (-1.68, -0.58)] are significantly less with duloxetine (p-value < 0.05). Time to first rescue analgesia was significantly more in patients where duloxetine was administered [1.27 (1.10, 1.45); p-value > 0.05]. Opioid consumption up to 24 h [-1.82 (-2.46, -1.18)] and 48 h [-2.48 (-3.46, -1.50)] was significantly less (p-value < 0.05) in patients who received duloxetine. Complications and recovery profiles were similar in patients receiving either duloxetine or a placebo.
INTERPRETATION
Based on GRADE findings, we conclude that there is low to moderate evidence to advocate the use of duloxetine for managing postoperative pain. Further trials are needed to replicate or refute these results based on robust methodology.
Topics: Humans; Analgesics, Opioid; Pain Management; Duloxetine Hydrochloride; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37246352
DOI: 10.1111/papr.13253 -
Current Opinion in Psychiatry Jan 2016Cognitive dysfunction in major depressive disorder (MDD) is common, pervasive across multiple subdomains of cognitive function, and is a principle determinant of health... (Review)
Review
PURPOSE OF REVIEW
Cognitive dysfunction in major depressive disorder (MDD) is common, pervasive across multiple subdomains of cognitive function, and is a principle determinant of health outcomes from patient, provider, and societal perspectives. The overarching aim herein is to provide rationale for the evaluation, measurement, and specific treatment of cognitive function in adults with MDD.
RECENT FINDINGS
Evidence indicates that cognitive dysfunction in MDD is a critical mediator of workplace disability. Systematic evaluation and measurement of cognitive function is warranted. All individuals with MDD should be evaluated for both objective and subjective cognitive dysfunction. Although differences between antidepressants in overall antidepressant efficacy are not consistent, unequivocal differences in improving measures of cognitive function are noted with evidence indicating that vortioxetine has multidomain cognitive benefits, whereas duloxetine has replicated evidence of improving measures of acquisition and recall (i.e. memory).
SUMMARY
The probability of functional recovery in MDD is likely to increase with interventions that specifically target and improve measures of cognitive function. Clinicians are encouraged to evaluate patients using a validated measure (e.g. the THINC-it tool); prevention of cognitive impairment in MDD is a critical therapeutic priority. Vortioxetine and duloxetine benefit measures of cognitive function in MDD. Preliminary evidence of beneficial effects on cognitive emotional processing are reported with ketamine.
Topics: Antidepressive Agents; Cognition; Cognition Disorders; Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Learning; Mental Recall; Piperazines; Recovery of Function; Serotonin and Noradrenaline Reuptake Inhibitors; Sulfides; Vortioxetine
PubMed: 26575300
DOI: 10.1097/YCO.0000000000000221 -
Chirality Mar 2024Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the... (Review)
Review
Given the markedly different pharmacological activities between enantiomeric isomers, it is crucial to encourage the stereoselective determination of chiral drugs in the biological and pharmaceutical fields, and the combination of drugs makes this analysis more complicated and challenging. Herein, a capillary electrophoresis (CE) method for the enantioseparation of ofloxacin and duloxetine was established, enabling the simultaneous identification of four isomers in nonracemic mixtures with enantiomeric excess (ee%) values exceeding 5%. This was achieved through the integration of theoretical simulation and electron circular dichroism (ECD), all without reliance on individual standards. Molecular modeling explained and verified the migration time differences of these isomers in electrophoretic separation. Moreover, the correlation coefficients (R ) between the enantiomeric peak area differentials and ee% were both above 0.99. Recovery rates were quantified using bovine serum as the matrix, with results ranging from 93.32% to 101.03% (RSD = 0.030) and 92.69% to 100.52% (RSD = 0.028) for these two chiral drugs at an ee value of 23.1%, respectively.
Topics: Duloxetine Hydrochloride; Ofloxacin; Stereoisomerism; Electrophoresis, Capillary
PubMed: 38454837
DOI: 10.1002/chir.23661