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Expert Opinion on Drug Metabolism &... Nov 2010Cyclobenzaprine immediate-release (CIR) is a widely prescribed skeletal muscle relaxant with an established efficacy and safety profile in patients with muscle spasm... (Comparative Study)
Comparative Study Review
IMPORTANCE OF THE FIELD
Cyclobenzaprine immediate-release (CIR) is a widely prescribed skeletal muscle relaxant with an established efficacy and safety profile in patients with muscle spasm associated with acute, painful conditions, although it is commonly associated with sedation. CIR is typically prescribed at a dosage of 10 mg three-times-daily. This review focuses on the pharmacokinetic profile of a new formulation, cyclobenzaprine extended-release (CER), which delivers a sustained plasma cyclobenzaprine concentration over 24 h, allowing once-daily dosing.
AREAS COVERED IN THIS REVIEW
Results from CER pharmacokinetic studies conducted through August 2010 are summarized.
WHAT THE READER WILL GAIN
This review provides information on the first four studies assessing the single-dose and steady-state pharmacokinetic profile of CER.
TAKE HOME MESSAGE
Once-daily CER 30 mg and three-times-daily CIR 10 mg produced comparable systemic exposures to cyclobenzaprine, but pharmacokinetic profiles were qualitatively different. CER was characterized by a single daily peak in cyclobenzaprine concentration versus three peaks/day for CIR. With once-daily dosing of CER, cyclobenzaprine concentration is sustained over 24 h. CER 30 mg provides approximately twice the exposure as CER 15 mg. Systemic exposure to CER is increased in the presence of food and in elderly subjects. Steady-state is achieved by day 7 of dosing.
Topics: Aged; Amitriptyline; Animals; Delayed-Action Preparations; Drug Administration Schedule; Food-Drug Interactions; Humans; Muscle Relaxants, Central; Randomized Controlled Trials as Topic; Spasm
PubMed: 20883117
DOI: 10.1517/17425255.2010.523419 -
Clinical Pharmacokinetics 1985In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While... (Review)
Review
In this article, studies on the disposition of amitriptyline after administration of a single dose, as well as following long term administration are reviewed. While long term studies showed bias towards a higher mean apparent oral clearance, studies in normal subjects nevertheless indicated a higher apparent oral clearance than that calculated from steady-state concentrations in depressed patients. Methodological issues could account for some of the discrepancies in mean values of the pharmacokinetic parameters of amitriptyline. Broad individual variability in the elimination rate of amitriptyline has been confirmed but could not be attributed to the clinical characteristics of the subjects.
Topics: Amitriptyline; Depressive Disorder; Half-Life; Humans; Kinetics; Models, Biological; Nortriptyline
PubMed: 3893842
DOI: 10.2165/00003088-198510030-00005 -
Analytical and Bioanalytical Chemistry Sep 2009A novel method based on solid-phase extraction was studied for the extraction of amitrole (3-amino-1,2,4-triazole), and its residue determination in apples has been...
A novel method based on solid-phase extraction was studied for the extraction of amitrole (3-amino-1,2,4-triazole), and its residue determination in apples has been developed. The samples were derivatized with 4-chloro-3,5-dinitrobenzotrifluoride (CNBF). The derivatization conditions and the influence of elution composition on the separation were investigated. In pH 9.5 H(3)BO(3)-Na(2)B(4)O(7) media, the reaction of amitrole with CNBF was complete at 60 degrees C after 30 min. The separation of derivatized amitrole was achieved at room temperature within 13 min by gradient elution mode with cetyltrimethylammonium bromide in mobile phase as ion-pair reagent. The method correlation coefficient was 0.9996, in concentrations ranging from 1.66 to 415 mg L(-1). The calculated recoveries of the proposed method were from 94.17% to 105.67%, and relative standard deviations were 1.57% to 6.44% in the application to the quantitative determination of amitrole in apples. The detection limit of amitrole was 0.10 mg L(-1) with a signal-to-noise ratio of 3.
Topics: Amitrole; Chromatography, High Pressure Liquid; Fluorobenzenes; Herbicides; Malus; Nitro Compounds; Sensitivity and Specificity; Solid Phase Extraction
PubMed: 19633831
DOI: 10.1007/s00216-009-2962-y -
Mycopathologia Oct 1976Cytokinin activity in extracts from actively growing cultures of Schizosaccharomyces octosporus was greatly reduced by exposure to amitrole (5 X 10--3M). Amitrole...
Cytokinin activity in extracts from actively growing cultures of Schizosaccharomyces octosporus was greatly reduced by exposure to amitrole (5 X 10--3M). Amitrole treatment, at the same concentration, stimulated cell enlargment and ascus production in this organism. These data suggest that a relationship may exist between low levels of endogenous cytokinins, cell expansion in preference to cell division, and ascus formation.
Topics: Amitrole; Ascomycota; Cytokinins; Dose-Response Relationship, Drug; Plant Growth Regulators; Schizosaccharomyces; Triazoles
PubMed: 995171
DOI: 10.1007/BF00627876 -
Fundamental and Applied Toxicology :... Jul 1994Amitrole, a widely used herbicide found to produce thyroid and liver tumors in rodents and classified as possibly carcinogenic to humans, was investigated to acquire...
Amitrole, a widely used herbicide found to produce thyroid and liver tumors in rodents and classified as possibly carcinogenic to humans, was investigated to acquire further information about its mechanism of action. A 20-hr exposure to amitrole concentrations ranging from 5.6 to 18 mM did not induce DNA fragmentation, as measured by the alkaline elution technique, in primary cultures of human thyroid follicular cells and of human liver cells. Under the same experimental conditions a minimal frequency of DNA breaks was detected in primary cultures of rat hepatocytes, but this event was presumably the unspecific consequence of a cytotoxic effect. In rats given amitrole with drinking water for 12 successive days at a daily dose of approximately 200 mg/kg, plasma levels of triiodothyronine and thyroxine displayed a progressive reduction, and a concurrent increase of both the mitotic index and frequency of S-phase cells revealing a clear-cut follicular cell hyperplasia was observed. In a group of these rats euthanized after 8 days of treatment any evidence of DNA fragmentation was absent in both thyroid and liver cells. Taken as a whole these results provide further evidence that the mechanism of amitrole carcinogenic activity is most likely nongenotoxic but due to hormone imbalance.
Topics: Adult; Amitrole; Animals; Carcinogens; Cell Survival; Cells, Cultured; DNA; Female; Humans; Liver; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Thyroid Gland
PubMed: 7958553
DOI: 10.1006/faat.1994.1085 -
Nature Mar 1977
Topics: Amitrole; Bacteria; Soil Microbiology; Triazoles
PubMed: 859587
DOI: 10.1038/266164a0 -
The Urologic Clinics of North America Feb 1994Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may... (Review)
Review
Limited data and an accumulated body of anecdotal experience with the tricyclic class of antidepressants suggest that this group of drugs (especially amitriptyline) may be an effective treatment modality in nonulcerative interstitial cystitis. Both the ease of administration and the relatively rapid onset of relief make these types of drugs appropriate to consider for first-line therapy after bladder distention has failed.
Topics: Amitriptyline; Animals; Clinical Trials as Topic; Cystitis; Humans
PubMed: 8284851
DOI: No ID Found -
Biological Research in Pregnancy and... 1983The mouse species is biologically characterized by a short gestation period that precludes completion of the intrauterine development before birth. Thus, in the mouse...
The mouse species is biologically characterized by a short gestation period that precludes completion of the intrauterine development before birth. Thus, in the mouse the late phase of intrauterine development is carried over into the postnatal age period. For this reason, we studied chemically induced hepatocarcinogenesis in B6C3F1 mice that were exposed transplacentally, postnatally, or during adulthood to benzidine x 2HCl, safrole, amitrol, ethylnitrosourea (ENU), and diethylnitrosamine (DEN). Data showed that perinatal exposure to those agents were significantly more hepatocarcinogenic than similar adult exposure. As regards the perinatally treated animals, the infants were shown to be more responsive than fetuses. The discussion shows that the higher "susceptibility" of infants was causally related to the presence of enzymatic complement required for the activation of procarcinogens and the concurrent high rate of macromolecular replication. It has been concluded that carcinogenesis in infants may be viewed as a part of the late "intrauterine" development. Thus, observed carcinogenicity has been construed as being relevant to the potential risk that might occur in other species exposed to these carcinogens during the late phase of intrauterine life.
Topics: Age Factors; Amitrole; Animals; Animals, Newborn; Carcinogens; Carcinoma, Hepatocellular; Female; Gestational Age; Liver Neoplasms; Male; Mice; Neoplasms, Experimental; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 6303459
DOI: No ID Found -
American Journal of Physiology. Cell... Jun 2023Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome....
Traditionally prescribed for mood disorders, tricyclic antidepressants (TCAs) have shown promising therapeutic effects on chronic neuralgia and irritable bowel syndrome. However, the mechanism by which these atypical effects manifest is unclear. Among the proposed mechanisms is the well-known pain-related inhibitory G-protein coupled receptor, namely the opioid receptor (OR). Here, we confirmed that TCA indeed stimulates OR and regulates the gating of TRPC4, a downstream signaling of the G-pathway. In an ELISA to quantify the amount of intracellular cAMP, a downstream product of OR/G-pathway, treatment with amitriptyline (AMI) showed a decrease in [cAMP] similar to that of the μOR agonist. Next, we explored the binding site of TCA by modeling the previously revealed ligand-bound structure of μOR. A conserved aspartate residue of ORs was predicted to participate in salt bridge interaction with the amine group of TCAs, and in aspartate-to-arginine mutation, AMI did not decrease the FRET-based binding efficiency between the ORs and Gα. As an alternative way to monitor the downstream signaling of G-pathway, we evaluated the functional activity of TRPC4 channel, as it is well known to be activated by Gα. TCAs increased the TRPC4 current through ORs, and TCA-evoked TRPC4 activation was abolished by an inhibitor of Gα or its dominant-negative mutant. As expected, TCA-evoked activation of TRPC4 was not observed in the aspartate mutants of OR. Taken together, OR could be proclaimed as a promising target among numerous binding partners of TCA, and TCA-evoked TRPC4 activation may help to explain the nonopioid analgesic effect of TCA. Endogenous opioid systems modulate pain perception, but concerns about opioid-related substance misuse limit their use. This study has raised TRPC4 channel as a candidate target for alternative analgesics, tricyclic antidepressants (TCAs). TCAs have been shown to bind to and activate opioid receptors (ORs), leading to downstream signaling pathways involving TRPC4. The functional selectivity and biased agonism of TCA towards TRPC4 in dependence on OR may provide a better understanding of its efficacy or side effects.
Topics: Antidepressive Agents, Tricyclic; Analgesics, Opioid; Aspartic Acid; Ligands; Carrier Proteins; Amitriptyline; Receptors, Opioid
PubMed: 37154492
DOI: 10.1152/ajpcell.00535.2022 -
Water Research Jul 2007This study investigated the removal of the herbicides diuron and amitrole from water under static and dynamic conditions using different activated carbons in the form of...
This study investigated the removal of the herbicides diuron and amitrole from water under static and dynamic conditions using different activated carbons in the form of fibers, cloth, and grains. In all cases, there was much greater adsorption of diuron than of amitrole due to the lower solubility, greater hydrophobicity, and larger dipolar moment of the former. The activated carbon cloth was the best adsorbent for diuron under dynamic conditions because it had the largest mesopore volume, water-accessible pore volume, and surface area. However, the best adsorbent for amitrole under dynamic conditions was the granular activated carbon due to its higher surface basicity. Comparisons using the best adsorbent for each herbicide showed that diuron was removed by the activated carbon more efficiently compared with amitrole under both dynamic and static conditions.
Topics: Adsorption; Amitrole; Carbon; Diuron; Herbicides; Hydrogen-Ion Concentration; Temperature; Water; Water Pollutants, Chemical; Water Pollution, Chemical; Water Purification
PubMed: 17434563
DOI: 10.1016/j.watres.2007.02.059