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Drug Design, Development and Therapy 2020This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study compares the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of amitriptyline hydrochloride tablets, and assesses the bioequivalence of the two products in healthy Chinese volunteers to obtain sufficient evidence for the marketing approval of the generic drug.
MATERIALS AND METHODS
A randomized, open-label, two-period crossover study (clinicaltrials.gov, NCT03646526) was conducted under both fasting and fed conditions in healthy Chinese volunteers (24 subjects/condition). Eligible subjects randomly received a single 25 mg dose of either the test or the reference formulation, followed by a 3-week washout period. Blood samples were collected until 144 h following administration. The pharmacokinetic parameters were acquired based on the concentration-time profiles, including the areas under the plasma concentration-time curve (AUC, AUC), the peak plasma concentration (C), the time to achieve C (T), and the elimination half-life (t). The geometric mean ratios (GMRs) and the corresponding 90% confidence intervals (CIs) of amitriptyline were acquired for bioequivalence analysis, and values of these parameters for nortriptyline were used for comparison of therapeutic outcomes. Safety assessments included laboratory tests, physical examination, vital signs, and incidence of adverse events (AEs).
RESULTS
The values of t and T for amitriptyline were not significantly different between the test and reference products under both fasting and fed conditions (P > 0.05). The GMRs of C, AUC, and AUC between the two products, and corresponding 90% CIs, were all within the range of 80% to 125% under both fasting and fed conditions. The test and reference products were well tolerated and did not elicit serious adverse events.
CONCLUSION
This study demonstrated that the generic and reference products were well tolerated by the subjects and bioequivalent, according to the rate and extent of the drug absorption.
Topics: Administration, Oral; Adolescent; Adult; Amitriptyline; Area Under Curve; Asian People; Cross-Over Studies; Drug Tolerance; Drugs, Generic; Fasting; Female; Healthy Volunteers; Humans; Male; Middle Aged; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 32801649
DOI: 10.2147/DDDT.S258173 -
Proceedings of the Royal Society of... Mar 1973
Review
Topics: Amitriptyline; Anthracenes; Antidepressive Agents; Anxiety; Diazepam; Dibenzazepines; Humans; Lactates; Limbic System; Monoamine Oxidase Inhibitors; Perphenazine; Psychosurgery
PubMed: 4572667
DOI: No ID Found -
Sensors (Basel, Switzerland) Oct 2022There is growing demand for rapid, nondestructive detection of trace-level bioactive molecules including medicines, toxins, biomolecules, and single cells, in a variety...
There is growing demand for rapid, nondestructive detection of trace-level bioactive molecules including medicines, toxins, biomolecules, and single cells, in a variety of disciplines. In recent years, surface-enhanced Raman scattering has been increasingly applied for such purposes, and this area of research is rapidly growing. Of particular interest is the detection of such compounds in dried saliva spots (DSS) and dried blood spots (DBS), often in medical scenarios, such as therapeutic drug monitoring (TDM) and disease diagnosis. Such samples are usually analyzed using hyphenated chromatography techniques, which are costly and time consuming. Here we present for the first time a surface-enhanced Raman spectroscopy protocol for the detection of the common antidepressant amitriptyline (AMT) on DBS and DSS using a test substrate modified with silver nanoparticles. The validated protocol is rapid and non-destructive, with a detection limit of 95 ppb, and linear range between 100 ppb and 1.75 ppm on the SERS substrate, which covers the therapeutic window of AMT in biological fluids.
Topics: Spectrum Analysis, Raman; Amitriptyline; Silver; Metal Nanoparticles; Saliva
PubMed: 36365956
DOI: 10.3390/s22218257 -
Acta Dermato-venereologica Jun 2024This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine... (Comparative Study)
Comparative Study
This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.
Topics: Humans; Retrospective Studies; Pruritus; Female; Male; Tertiary Care Centers; Middle Aged; Treatment Outcome; Amitriptyline; Lidocaine; Ketamine; Pregabalin; Aged; Drug Therapy, Combination; Adult; Antipruritics; Florida; Skin Cream; Administration, Cutaneous; Electronic Health Records
PubMed: 38916180
DOI: 10.2340/actadv.v104.40246 -
Kardiologia Polska 2013
Topics: Amitriptyline; Antidepressive Agents, Tricyclic; Bundle-Branch Block; Humans; Male; Syncope
PubMed: 23797444
DOI: 10.5603/KP.2013.0135 -
PloS One 2020Inappropriate medication use is a major patient safety concern, especially for the elderly population. Amitriptyline is widely used in primary care in South Africa and a...
BACKGROUND
Inappropriate medication use is a major patient safety concern, especially for the elderly population. Amitriptyline is widely used in primary care in South Africa and a cross-sectional study found that amitriptyline was prescribed potentially inappropriately in 6.5% of elderly patients. An analysis of prescriptions from the Chronic Dispensing Unit in the Western Cape revealed that amitriptyline was one of the most common medicines prescribed without a suitable diagnosis listed on the prescription.
OBJECTIVE
The main objective of the medicine use evaluation (MUE) was to determine whether amitriptyline was prescribed in accordance with recommendations from standard treatment guidelines (STG) and essential medicines lists (EML) endorsed by the National Department of Health, South Africa.
METHODS
A retrospective, cross-sectional, multicentre review of patients' clinical notes was conducted. The study population was selected by systematic random sampling from adult outpatients who were prescribed amitriptyline for longer than three months. Criteria for evaluation included amitriptyline indication and total daily dose prescribed.
RESULTS
Of the sample of 2237 patient medical records reviewed, 1732 (77.4%) included amitriptyline prescriptions that were according to the approved STG indications. For the approved STG indications, amitriptyline was prescribed mainly for osteoarthritis (25.8%), neuropathies (18.5%) and chronic non-cancer pain (17.9%). Major depressive disorders constituted only 8.6% of the patient records reviewed; however, doses were atypically low. The main inappropriate indication for amitriptyline was sleep disorders (16%).
CONCLUSION
This MUE has highlighted the need to improve the use of amitriptyline in specific patient populations, e.g. the elderly and patients with sleeping disorders.
Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Analgesics, Non-Narcotic; Chronic Pain; Female; Hospitals, Public; Humans; Inappropriate Prescribing; Male; Middle Aged; Osteoarthritis; Sleep Wake Disorders; South Africa
PubMed: 32311002
DOI: 10.1371/journal.pone.0231675 -
Behavioural Brain Research May 2014Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like...
Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments.
Topics: Amitriptyline; Analgesics, Non-Narcotic; Animals; Arthritis; Carrageenan; Disease Models, Animal; Exploratory Behavior; Food Preferences; Hyperalgesia; Kaolin; Male; Maze Learning; Mood Disorders; Motor Activity; Pain Threshold; Physical Stimulation; Rats; Rats, Wistar; Swimming
PubMed: 24518202
DOI: 10.1016/j.bbr.2014.02.003 -
International Journal of Nanomedicine 2017The 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...
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. Through the entrapment study, squarticles could intercept 40%-50% of the amitriptyline during 2 h with low leakage after loading into the nanoparticles. The results of isothermal titration calorimetry demonstrated greater interaction of amitriptyline with the surface of anionic squarticles ( =28,700) than with cationic ones ( =5,010). Real-time imaging showed that intravenous administration of anionic squarticles resulted in a prolonged retention in the circulation. In a rat model of amitriptyline poisoning, anionic squarticles increased the plasma drug concentration by 2.5-fold. The drug uptake in the highly perfused organs was diminished after squarticle infusion, indicating the lipid sink effect of bringing the entrapped overdosed drug in the tissues back into circulation. In addition, the anionic nanosystems restored the mean arterial pressure to near normal after amitriptyline injection. The survival rate of overdosed amitriptyline increased from 25% to 75% by treatment with squarticles. Our results show that the adverse effects of amitriptyline intoxication could be mitigated by administering anionic squarticles. This lipid nanoemulsion is a potent antidote to extract amitriptyline and eliminate it.
Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Antidotes; Drug Overdose; Inactivation, Metabolic; Male; Nanoparticles; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 29138563
DOI: 10.2147/IJN.S143370 -
The Acid Sphingomyelinase Inhibitor Amitriptyline Ameliorates TNF-α-Induced Endothelial Dysfunction.Cardiovascular Drugs and Therapy Feb 2024Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in...
PURPOSE
Inflammation associated endothelial cell (EC) dysfunction is key to atherosclerotic disease. Recent studies have demonstrated a protective role of amitriptyline in cardiomyocytes induced by hypoxia/reoxygenation. However, the mechanism by which amitriptyline regulates the inflammatory reaction in ECs remains unknown. Thus, the aim of this study was to investigate whether amitriptyline protects against inflammation in TNF-α-treated ECs.
METHODS
HUVECs were incubated with amitriptyline (2.5 μM) or TNF-α (20 ng/ml) for 24 h. EdU, tube formation, transwell, DHE fluorescence staining, and monocyte adhesion assays were performed to investigate endothelial function. Thoracic aortas were isolated from mice, and vascular tone was measured with a wire myograph system. The levels of ICAM-1, VCAM-1, MCP-1, phosphorylated MAPK and NF-κB were detected using western blotting.
RESULTS
Amitriptyline increased the phosphorylation of nitric oxide synthase (eNOS) and the release of NO. Amitriptyline significantly inhibited TNF-α-induced increases in ASMase activity and the release of ceramide and downregulated TNF-α-induced expression of proinflammatory proteins, including ICAM-1, VCAM-1, and MCP-1 in ECs, as well as the secretion of sICAM-1 and sVCAM-1. TNF-α treatment obviously increased monocyte adhesion and ROS production and impaired HUVEC proliferation, migration and tube formation, while amitriptyline rescued proliferation, migration, and tube formation and decreased monocyte adhesion and ROS production. Additionally, we demonstrated that amitriptyline suppressed TNF-α-induced MAPK phosphorylation as well as the activity of NF-κB in HUVECs. The results showed that the relaxation response of aortic rings to acetylcholine in the WT-TNF-α group was much lower than that in the WT group, and the sensitivity of aortic rings to acetylcholine in the WT-TNF-α group and WT-AMI-TNF-α group was significantly higher than that in the WT-TNF-α group.
CONCLUSION
These results suggest that amitriptyline reduces endothelial inflammation, consequently improving vascular endothelial function. Thus, the identification of amitriptyline as a potential strategy to improve endothelial function is important for preventing vascular diseases.
Topics: Animals; Mice; Humans; NF-kappa B; Intercellular Adhesion Molecule-1; Tumor Necrosis Factor-alpha; Human Umbilical Vein Endothelial Cells; Amitriptyline; Reactive Oxygen Species; Vascular Cell Adhesion Molecule-1; Sphingomyelin Phosphodiesterase; Acetylcholine; Inflammation; Vascular Diseases
PubMed: 36103099
DOI: 10.1007/s10557-022-07378-0 -
British Journal of Pharmacology Jun 2022Inwardly rectifying K (K ) channels located on the basolateral membrane of epithelial cells of the distal nephron play a crucial role in K handling and BP control,...
BACKGROUND AND PURPOSE
Inwardly rectifying K (K ) channels located on the basolateral membrane of epithelial cells of the distal nephron play a crucial role in K handling and BP control, making these channels an attractive target for the treatment of hypertension. The purpose of the present study was to determine how the inhibition of basolateral K 4.1/K 5.1 heteromeric K channel affects epithelial sodium channel (ENaC)-mediated Na transport in the principal cells of cortical collecting duct (CCD).
EXPERIMENTAL APPROACH
The effect of fluoxetine, amitriptyline and recently developed K inhibitor, VU0134992, on the activity of K 4.1, K 4.1/K 5.1 and ENaC were tested using electrophysiological approaches in CHO cells transfected with respective channel subunits, cultured polarized epithelial mCCD cells and freshly isolated rat and human CCD tubules. To test the effect of pharmacological K 4.1/K 5.1 inhibition on electrolyte homeostasis in vivo and corresponding changes in distal tubule transport, Dahl salt-sensitive rats were injected with amitriptyline (15 mg·kg ·day ) for 3 days.
KEY RESULTS
We found that inhibition of K 4.1/K 5.1, but not the K 4.1 channel, depolarizes the cell membrane, induces the elevation of intracellular Ca concentration and suppresses ENaC activity. Furthermore, we demonstrate that amitriptyline administration leads to a significant drop in plasma K level, triggering sodium excretion and diuresis.
CONCLUSION AND IMPLICATIONS
The present data uncover a specific role of the K 4.1/K 5.1 channel in the modulation of ENaC activity and emphasize the potential for using K 4.1/K 5.1 inhibitors to regulate electrolyte homeostasis and BP.
Topics: Amitriptyline; Animals; Cricetinae; Cricetulus; Electrolytes; Epithelial Sodium Channels; Kidney Tubules, Collecting; Potassium Channels, Inwardly Rectifying; Rats; Rats, Inbred Dahl; Sodium
PubMed: 34904226
DOI: 10.1111/bph.15779