Duloxetine
- CAS NO.:116539-59-4
- Empirical Formula: C18H19NOS
- Molecular Weight: 297.41
- MDL number: MFCD06801358
- EINECS: 601-438-0
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-03-19 15:37:51
What is Duloxetine?
Absorption
Duloxetine is incompletely absorbed with a mean bioavailability of 50% although there is wide variability in the range of 30-80%. The population absorption constant (ka) is 0.168 h-1.The molecule is susceptible to hydrolysis in acidic environments necessitating the use of an enteric coating to protect it during transit through the stomach. This creates a 2 hour lag time from administration to the start of absorption. The Tmax is 6 hours including the lag time. Administering duloxetine with food 3 hour delay in Tmax along with an 10% decrease in AUC. Similarly, administering the dose at bedtime produces a 4 hour delay and 18% decrease in AUC with a 29% reduction in Cmax. These are attributed to delayed gastric emptying in both cases but are not expected to impact therapy to a clinically significant degree.
Toxicity
Overdose
Fatalities have been reported with doses of 1000mg involving both mixed drugs as well as duloxetine alone. Signs and symptoms of overdose include: somnolence, coma, serotonin syndrome, seizure, syncope, hypo- or hypertension, tachycardia, and vomiting. No antidote exists and the drug is unlikely to be cleared by hemodialysis. Supportive care is recommended along with activated charcoal and gastric lavage to reduce absorption. If serotonin syndrome occurs specific treatment such as temperature control or cyproheptadine may be initiated.
Carcinogenicity & Mutagenicity
Increased incidence of hepatocellular carcinomas and adenomas were reported in female mice fed 140 mg/kg/day duloxetine for 2 years, equivalent to 6 times the maximum recommended human dose (MRHD). No effect was reported with doses of 50mg/kg/day (2 time MRHD) in females or 100 mg/kg/day in males (4 times MRHD). Similar investigation in rats produced no carcinogenicity at doses of 27 mg/kg/day (2 times MRHD)in females and 36 mg/kg/day in males (4 times MRHD).
No mutagenicity, clastogenicity, induction of sister chromatid exchange, or genotoxicity has been observed in toxicology investigations.
Reproductive Toxicity
Neither male or female rats displayed adverse reproductive effects at doses up to 45 mg/kg/day (4 times MRHD).
Lactation
An estimated 25% of plasma duloxetine appears in breast milk with the estimated daily infant dose being 0.14% of the maternal dose. Breast milk concentrations have been observed to peak 3 hours after administration.
The Uses of Duloxetine
Antidepressant.
Background
Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor. It was originally discovered in 1993 and developed by Eli Lilly and Company as LY248686. Duloxetine first received approval from the FDA in August, 2004 as Cymbalta for the treatment of Major Depressive Disorder. It has since received approval for a variety of indications including the treatment of neuropathic pain, Generalized Anxiety disorder, osteoarthritis, and stress incontinence. Duloxetine continues to be investigated for the treatment of pain in cancer, surgery, and more.
Indications
Indicated for:
1) Management of Major Depressive Disorder.
2) Management of Generalized Anxiety Disorder.
3) Management of diabetic peripheral neuropathy.
4) Management of fibromyalgia.
5) Management of chronic musculoskeletal pain.
6) Management of osteoarthritis of the knee in adults.
7) Management of chronic lower back pain in adults.
8) Management of stress urinary incontinence in adult women.
Off-label uses include:
1) Management of chemotherapy-induced peripheral neuropathy.
2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete.
What are the applications of Application
Duloxetine is an inhibitor of ST and SLC6A2
Pharmacokinetics
Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter. This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores. It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg.
Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain. This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys.
While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained.
Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling.
Metabolism
Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6 with the former being the greater contributor. It is hydroxylated at the 4, 5, or 6 positions on the naphthalene ring with the 4-hydroxy metabolite proceeding directly to a glucuronide conjugate while the 5 and 6-hydroxy metabolites proceed through a catechol and a 5-hydroxy, 6-methoxy intermediate before undergoing glucuronide or sulfate conjugation. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in the feces but comprises <5% of the total excreted drug. Many other metabolites exist but have not been identified due their low contribution to the overall profile of duloxetine and lack of clinical significance.
Properties of Duloxetine
Boiling point: | 466.2±40.0 °C(Predicted) |
Density | 1.158±0.06 g/cm3(Predicted) |
Safety information for Duloxetine
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H302:Acute toxicity,oral H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation |
Precautionary Statement Codes |
P264:Wash hands thoroughly after handling. P264:Wash skin thouroughly after handling. P270:Do not eat, drink or smoke when using this product. P280:Wear protective gloves/protective clothing/eye protection/face protection. P302+P352:IF ON SKIN: wash with plenty of soap and water. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. P332+P313:IF SKIN irritation occurs: Get medical advice/attention. P337+P313:IF eye irritation persists: Get medical advice/attention. P501:Dispose of contents/container to..… |
Computed Descriptors for Duloxetine
Abamectin manufacturer
Ralington Pharma
Vijaya Pharma And Life Science
Aspen Biopharma Labs Pvt Ltd
New Products
3-N-BOC-(S)-AMINO BUTYRONITRILE 4-Piperidinopiperidine 2-Methyl-4-nitrobenzoic acid 2-(4-bromophenyl)-2-methylpropanoic acid 4-Acetyl-2-methylbenzoicacid Acetyl-meldrum's acid Ethyl-4-Pyrazole carboxylate 2,6 Di acetylpyridine 2,6-Pyridinedimethanol 5,7-Dichloro-3H-Imidazo[4,5-B]Pyridine 5-Bromo-2-Methoxy-4-Methyl-3-Nitropyridine 2-Fluoro-5-Iodopyridine 2-Fluoro-5-Methylpyridine 2-Chloro-3-Bromo-5-Amiopyridine METHYL-4-(BUTYRYLAMINO)3-METHYL-5-NITROBENZOATE TRANS-CYCLOBUTANE-1,2- DICARBOXYLIC ACID 5-Nitro indazole R-(-)-5-(2-AMINO-PROPYL)-2-METHOXY-BENZENESULFONAMIDE 1,3-cyclohexanedione 4-Aminophenaethylalchol 3-NITRO-5-ACETYL IMINODIBENZYL (S)-(+)-4-BENZYL-2-OXAZOLIDINONE 4-FLUORO PHENYL MAGNESIUM BROMIDE 1.0 M IN THF 1-HYDROXY-4-METHYL6-(2,4,4-TRI METHYL PHENYL)-2-PYRIDONE MONO ETHANOL AMINE(PIROCTONE OLAMINE)Related products of tetrahydrofuran
You may like
-
116539-59-4 Duloxetine 98%View Details
116539-59-4 -
116539-59-4 98%View Details
116539-59-4 -
116539-59-4 Duloxetine 98%View Details
116539-59-4 -
116539-59-4 98%View Details
116539-59-4 -
68915-31-1 99%View Details
68915-31-1 -
Azadirachtin 11141-17-6 99%View Details
11141-17-6 -
Geraniol 99%View Details
106-24-1 -
BENZALKONIUM CHLORIDE BKC 99%View Details
8001-54-5