serotonin reuptake; norepinephrine reuptake

Duloxetine is a pretreat of norepinephrine reuptake and serotonin (5-HT). Duloxetine has a weaker inhibitory effect on dopamine reuptake when compared to its effects on 5-HT and norepinephrine reuptake. It also exhibits low binding affinity for other neurotransmitter receptors, such as opioid receptors, dopamine D2 receptors, adrenergic, muscarinic (nonselective), and histamine H1 receptors. More than 90% of duloxetine in human plasma is protein bound, according to in vitro research. A1-acid glycoprotein and albumin are the main targets of the binding[1].

Maximum plasma concentration (Cmax) of duloxetine ranges from about 47 ng/mL (40 mg twice-daily dose) to 110 ng/mL (80 mg twice-daily dose) about 6 hours after dosing. Duloxetine has an elimination half-life of roughly 10–12 hours and a distribution volume of about 1640 L. After a 60 mg single dose, the absolute oral bioavailability ranged from 30% to 80% on average in one study and from 19% to 71% on average in another. Duloxetine absorption is influenced by food and time of day; food and bedtime administration cause a 4-hour tmax delay[1].

Cell Viability Assay[2] Cells were seeded in 96-well plates at a density of 2 × 105 cells per well, grown for 24 h, and then treated with the drugs according to time-dependence or dose-dependence protocols. Each treatment was conducted in triplicate. After the drug treatments, the cell viability was assayed using a Cell Counting Kit-8 (CCK-8) according to the manufacturer’s instructions. CCK-8 uses the sensitive colorimetric WST-8 assay to determine the number of viable cells. WST-8 is a highly water-soluble tetrazolium salt, with the chemical designation of 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt

Duloxetine and α-Adrenergic Receptor Antagonists Administration[3] Duloxetine was dissolved in distilled water (D.W.). Different doses of duloxetine (10, 30, and 60 mg/kg) were administered (i.p.). To test which adrenergic receptor subtypes mediated the anti-allodynic effects of duloxetine in oxaliplatin-administered mice, antagonists were administered intrathecally 20 min prior to duloxetine treatments. Non-selective α-adrenergic antagonists (phentolamine, 20 μg), α1-adrenergic receptor antagonists (prazosin, 10 μg), and α2-adrenergic receptor antagonists (idazoxan, 10 μg) were administered in volumes of 5 μL. The dose of each antagonist was determined based on previously conducted studies showing the selective and effective antagonistic action against adrenergic receptor-mediated responses.[3]

Absorption, Distribution and Excretion
Duloxetine is not completely absorbed, with an average bioavailability of 50%, but individual variability is significant, ranging from 30% to 80%. The population absorption constant (ka) is 0.168 h⁻¹. The molecule is readily hydrolyzed in acidic environments, thus requiring enteric coating to protect it from degradation as it passes through the stomach. This results in a 2-hour delay from administration to the onset of absorption. The time to peak absorption (Tmax) is 6 hours, including the delay. Taking duloxetine with food delays Tmax by 3 hours and reduces AUC by 10%. Similarly, taking it at bedtime delays Tmax by 4 hours, reduces AUC by 18%, and reduces Cmax by 29%. Both of these are attributed to delayed gastric emptying but are not expected to have a significant impact on clinical treatment. Approximately 70% of duloxetine is excreted primarily in the urine as a conjugated metabolite. Another 20% is present in the feces as the parent drug, a 4-hydroxy metabolite, and an unidentified metabolite. Because fecal excretion time exceeds normal gastrointestinal transit time, bile secretion is believed to play a role. The apparent volume of distribution is 1620–1800 liters. Duloxetine can cross the blood-brain barrier and accumulates in the cerebral cortex at concentrations higher than plasma concentrations. The clearance of duloxetine has been reported to vary considerably among individuals, ranging from 57–114 liters/hour. Steady-state plasma concentrations remain dose-dependent; increases in dose from 30 mg to 60 mg and from 60 mg to 120 mg resulted in a 2.3-fold and 2.6-fold increase in steady-state plasma concentration (Css), respectively. Multiple metabolites have been identified in urine, some representing only minor elimination pathways. Only trace amounts (<1% of the dose) of unmetabolized duloxetine are present in urine. The majority (approximately 70%) of the duloxetine dose appears in urine as metabolites; approximately 20% is excreted in feces. Duloxetine is extensively metabolized, but its major circulating metabolites have not been shown to significantly contribute to its pharmacological activity. The elimination half-life of duloxetine is approximately 12 hours (range 8 to 17 hours), and its pharmacokinetics are dose-dependent within the therapeutic range. Steady-state plasma concentrations are typically reached 3 days after administration. Duloxetine is primarily eliminated via hepatic metabolism, involving two P450 isoenzymes, CYP1A2 and CYP2D6. Oral absorption of duloxetine hydrochloride is good. The median time to absorption (Tlag) is 2 hours, and peak plasma concentration (Cmax) of duloxetine is reached 6 hours after administration. Food does not affect the Cmax of duloxetine but delays the time to peak concentration from 6 hours to 10 hours and slightly reduces the extent of absorption (AUC) by approximately 10%. Compared to morning administration, evening administration delays absorption of duloxetine by 3 hours and increases apparent clearance by one-third. The average apparent volume of distribution is approximately 1640 L. Duloxetine has a high binding rate to human plasma proteins (>90%), primarily albumin and α1-acid glycoprotein. Interactions between duloxetine and other highly protein-bound drugs have not been fully assessed. Renal or hepatic impairment does not affect the plasma protein binding rate of duloxetine. Metabolism/Metabolites Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6, with CYP1A2 contributing more. It undergoes hydroxylation at positions 4, 5, or 6 of the naphthyl ring. The 4-hydroxy metabolite is directly converted to a glucuronide conjugate, while the 5- and 6-hydroxy metabolites first pass through catechol and 5-hydroxy, 6-methoxy intermediates before being converted to glucuronide or sulfate conjugates. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in feces, but it accounts for less than 5% of the total excreted drug. Many other metabolites exist, but they have not been identified due to their low contribution to the overall metabolite profile of duloxetine and lack of clinical significance. Following oral administration of 14C-labeled duloxetine, the biotransformation and distribution of duloxetine in humans have been determined. Duloxetine accounts for approximately 3% of the total radiolabeled material in plasma, indicating that it undergoes extensive metabolism, generating a variety of metabolites. The main biotransformation pathway of duloxetine involves the oxidation of the naphthyl ring, followed by conjugation and further oxidation. In vitro experiments have shown that both CYP1A2 and CYP2D6 can catalyze the oxidation of the naphthyl ring. Metabolites found in plasma include 4-hydroxyduloxetine glucoside and 5-hydroxy,6-methoxyduloxetine sulfate. Known human metabolites of duloxetine include 5-((S)-3-methylamino-1-thiophene-2-ylpropoxy)-naphth-2-ol, 5-hydroxyduloxetine, and 4-hydroxyduloxetine.
The major biotransformation pathway of duloxetine involves the oxidation of the naphthyl ring, followed by conjugation and further oxidation. Both CYP2D6 and CYP1A2 can catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxyduloxetine glucoside and 5-hydroxy,6-methoxyduloxetine sulfate. The major circulating metabolites have not been shown to significantly contribute to the pharmacological activity of duloxetine.
Elimination pathways: Several other metabolites have been identified in urine, some of which represent only minor elimination pathways. The majority (approximately 70%) of the duloxetine dose is excreted in urine as metabolites; approximately 20% is excreted in feces.
Half-life: 12 hours (range 8–17 hours)
Biological half-life
Mean 12 hours, range 8–17 hours.
The elimination half-life of duloxetine is approximately 12 hours (range 8–17 hours), and its pharmacokinetics are dose-dependent within the therapeutic range.

Toxicity Summary
Identification and Uses: Duloxetine hydrochloride is used for the acute treatment of generalized anxiety disorder in adults, the treatment of neuropathic pain associated with diabetic peripheral neuropathy in adults, the treatment of fibromyalgia in adults, the treatment of moderate to severe stress urinary incontinence (SUI) in women, and the acute and maintenance treatment of major depressive disorder in adults. Human Exposure and Toxicity: There is a potential risk of serious hepatotoxicity; elevated serum transaminase levels have been reported, sometimes requiring discontinuation of duloxetine. Post-marketing experience indicates that there have been reports of fatal acute overdose, primarily due to mixed overdose, but also including cases of duloxetine alone (dose as low as 1000 mg). Signs and symptoms of duloxetine overdose (alone or in combination with other drugs) include somnolence, coma, serotonin syndrome, seizures, syncope, tachycardia, hypotension, hypertension, and vomiting. A higher proportion of patients taking 120 mg duloxetine daily reported adverse events upon discontinuation compared to lower doses. In patients taking 40 to 120 mg duloxetine daily, the proportion reporting at least one adverse event following discontinuation was significantly different from the placebo group. Treatment with duloxetine for more than 8–9 weeks did not appear to increase the incidence or severity of adverse events following discontinuation. Abrupt discontinuation of duloxetine resulted in a series of adverse events similar to those of other selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SNRIs). Animal studies: Duloxetine was added to the diet of mice for 2 years. In female mice, daily intake of 140 mg/kg duloxetine (equivalent to 6 times the maximum recommended human dose (MRHD) of 120 mg/day on mg/m²) increased the incidence of hepatocellular adenomas and carcinomas. The no-effect dose was 50 mg/kg/day (equivalent to twice the MRHD). In male mice, daily intake of duloxetine up to 100 mg/kg (equivalent to 4 times the MRHD) did not increase tumor incidence. Oral treatment with duloxetine up to 45 mg/kg/day (equivalent to 4 times the maximum recommended human dose of MRHD) in male or female rats before and during mating did not alter mating behavior or fertility. When pregnant rats were treated with oral duloxetine during pregnancy and lactation, a dose of 30 mg/kg/day (equivalent to 5 times the maximum recommended human dose of MRHD, or twice the human dose of 120 mg/day on a mg/m² basis) reduced the survival rate of pups at 1 day after birth and their birth and lactation weight; the no-effect dose was 10 mg/kg/day. Furthermore, exposure of the mother to 30 mg/kg/day resulted in pups exhibiting behaviors consistent with increased responsiveness, such as enhanced startle response to noise and decreased motor habituation. Treatment of female mice with duloxetine did not adversely affect the growth and reproductive performance of their offspring after weaning. Duloxetine did not show mutagenicity in the Ames test for bacterial reverse mutation and did not show breakage in the in vivo chromosome aberration test in mouse bone marrow cells. Furthermore, duloxetine did not show genotoxicity in the in vitro mammalian forward mutation assay in mouse lymphoma cells or the in vitro unplanned DNA mutation assay in rat hepatocytes, and it also did not show mutagenicity in the in vivo sister chromatid exchange assay in hamster bone marrow cells. Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a weak inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, or GABA receptors. The antidepressant and analgesic effects of duloxetine are thought to be related to its enhancement of serotonergic and norepinephrine activity in the central nervous system. The mechanism of action of duloxetine in treating stress urinary incontinence (SUI) is not fully understood, but it is believed to be related to increased serotonin and norepinephrine activity in the spinal cord, thereby increasing urethral closure force and reducing involuntary urine leakage. Toxicity Data: Oral LD50 in rats: 491 mg/kg for males and 279 mg/kg for females (A308). Drug Interactions: In vitro studies have shown that duloxetine is an inhibitor of the CYP1A2 isoenzyme. Two clinical studies showed that when used in combination with duloxetine (60 mg twice daily), the mean increase in theophylline AUC (90% confidence interval) was 7% (1%–15%) and 20% (13%–27%), respectively. Platelet-released serotonin plays an important role in hemostasis. Epidemiological studies using case-control and cohort designs have confirmed an association between the use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding, and have shown that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin may enhance this bleeding risk. When selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs) are used in combination with warfarin, altered anticoagulation effects, including an increased risk of bleeding, have been reported. In healthy subjects (n=15), concomitant administration of warfarin (2–9 mg once daily) and duloxetine (60 or 120 mg once daily) for up to 14 days under steady-state conditions showed no significant change in the international normalized ratio (INR) from baseline (mean INR variation ranged from 0.05 to +0.07). Duloxetine had no effect on the total pharmacokinetic parameters (protein-bound drug plus free drug) of both R-warfarin and S-warfarin (AUCt,ss, Cmax,ss, or tmax,ss). Because duloxetine may affect platelets, patients receiving warfarin should be closely monitored when starting or stopping duloxetine. In subjects with impaired CYP2D6 metabolism (n=14), concomitant administration of duloxetine 40 mg (twice daily) and the potent CYP1A2 inhibitor fluvoxamine 100 mg resulted in a 6-fold increase in the AUC and Cmax of duloxetine. Concomitant administration of duloxetine (40 mg once daily) and paroxetine (20 mg once daily) increased the AUC concentration of duloxetine by approximately 60%, and the inhibitory effect is expected to increase with higher doses of paroxetine. Other potent CYP2D6 inhibitors (e.g., fluoxetine, quinidine) are expected to produce similar effects. When male subjects (n=14) were concurrently administered duloxetine 60 mg and the potent CYP1A2 inhibitor fluvoxamine 100 mg, the AUC of duloxetine increased approximately 6-fold, Cmax increased approximately 2.5-fold, and half-life (t1/2) increased approximately 3-fold. Other drugs that inhibit CYP1A2 metabolism include cimetidine and quinolone antibiotics such as ciprofloxacin and enoxacin.

[1]. Clin Pharmacokinet . 2011 May;50(5):281-94.

[2]. Duloxetine-Induced Neural Cell Death and Promoted Neurite Outgrowth in N2a Cells. Neurotox Res. 2020 Dec;38(4):859-870.
[3]. Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. Int J Mol Sci . 2017 Dec 5;18(12):2626.

Therapeutic Uses

Adrenergic reuptake inhibitors; analgesics; antidepressants; dopamine reuptake inhibitors; serotonin reuptake inhibitors.
Duloxetine hydrochloride is used for the acute and maintenance treatment of major depressive disorder in adults.
Duloxetine has been used to treat moderate to severe stress urinary incontinence (SUI) in women.
Duloxetine hydrochloride is used to treat fibromyalgia in adults.
For more complete data on the therapeutic uses of duloxetine (6 types), please visit the HSDB record page.

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Drug Warnings
/Black Box Warning/ Warning: Suicidal ideation and behavior: Short-term studies have shown that antidepressants increase the risk of suicidal ideation and behavior in children, adolescents, and young adults. These studies did not show an increased risk of suicidal ideation and behavior in patients aged 24 years and older; the risk was reduced in patients aged 65 years and older. Patients of all ages starting antidepressant treatment should be closely monitored for worsening of their condition and for the occurrence of suicidal ideation and behavior. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician.
Pregnancy grade C. Some newborns exposed to selective serotonin and norepinephrine reuptake inhibitors (SNRIs) or SNRIs during late pregnancy (third gestation) develop complications, sometimes severe, requiring prolonged hospitalization, respiratory support, enteral nutrition, and other forms of supportive care in a special care ward. These complications may occur immediately after delivery and usually last for several days or up to 2–4 weeks. To date, clinical manifestations in newborns have included respiratory distress, cyanosis, apnea, seizures, unstable or feverish body temperature, feeding difficulties, dehydration, excessive weight loss, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremors, irritability, lethargy, decreased or no response to painful stimuli, and persistent crying. These clinical features appear to be consistent with the direct toxic effects of SNRIs or may be drug withdrawal syndrome. It is worth noting that in some cases, the clinical presentation is consistent with serotonin syndrome (see “Drug Interactions: Drugs Associated with Serotonin Syndrome” in Fluoxetine Hydrochloride 28:16.04.20). Clinicians should carefully weigh the potential risks and benefits of duloxetine treatment in pregnant women during late pregnancy. If duloxetine is taken during pregnancy, a cautious, gradual reduction of the duloxetine dosage may be considered in the three months leading up to delivery. Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) (including duloxetine) or selective serotonin reuptake inhibitors (SSRIs) have been reported to cause potentially life-threatening serotonin syndrome, especially when taken concurrently with other serotonergic drugs (e.g., serotonin [5-HT] type 1 receptor agonists [“triptans”]) or drugs that impair serotonin metabolism (e.g., monoamine oxidase [MAO] inhibitors). Symptoms of serotonin syndrome may include altered mental status (e.g., agitation, hallucinations, coma), autonomic dysfunction (e.g., tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular abnormalities (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Concomitant use with monoamine oxidase inhibitors (MAOIs) used to treat depression is contraindicated. (See “Drug Interactions: Monoamine Oxidase Inhibitors”.) If clinical necessity dictates the use of duloxetine and a 5-HT1 receptor agonist, the patient should be closely monitored, especially at the beginning of treatment, at dose increases, or when starting other serotonergic drugs. Concomitant use of duloxetine and serotonin precursors (e.g., tryptophan) is not recommended. Liver failure, sometimes life-threatening, has been reported in patients treated with duloxetine. These cases presented with hepatitis, accompanied by abdominal pain, hepatomegaly, and significantly elevated serum transaminase levels (more than 20 times the upper limit of normal), with or without jaundice, reflecting mixed or hepatocellular liver injury. Duloxetine should be discontinued in any patient who develops jaundice or other clinically significant liver dysfunction; treatment should not be resumed unless another cause of liver dysfunction can be identified. For more complete data on duloxetine (18 total), please visit the HSDB records page.
Pharmacodynamics
Duloxetine enhances glutamatergic activation of the pudendal motor nerves innervating the external urethral sphincter by increasing the concentrations of serotonin and norepinephrine in the nucleus onnulucis. This enhanced signaling results in stronger sphincter contractions. Increased sphincter contraction increases the pressure required for stress urinary incontinence episodes. Studies have shown that duloxetine improves patients' overall improvement impression scores and urinary incontinence quality-of-life scores. Furthermore, studies have shown that 40 mg and 80 mg doses reduce the median frequency of urinary incontinence episodes. Duloxetine acts on the dorsal horn of the spinal cord, enhancing serotonergic and adrenergic pathways involved in descending pain inhibition. This leads to an increase in the activation threshold required to transmit pain stimuli to the brain, thus effectively relieving pain, especially neuropathic pain. Duloxetine has shown efficacy in various pain assessment methods, relieving pain in a variety of conditions, including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis. Although duloxetine has demonstrated efficacy in animal models of mood disorders and human clinical trials, its broad pharmacodynamic mechanism of action in regulating mood in the brain remains to be elucidated. Increased blood pressure is a common side effect of duloxetine due to vasoconstriction caused by enhanced norepinephrine signaling.

C18H19NOS

297.416

297.12

116539-59-4

Duloxetine hydrochloride; 136434-34-9; Duloxetine-d7; 919514-01-5; (±)-Duloxetine hydrochloride; 947316-47-4; Duloxetine metabolite Para-Naphthol Duloxetine; 949095-98-1

60835

Typically exists as solid at room temperature

1.2±0.1 g/cm3

466.2±40.0 °C at 760 mmHg

235.7±27.3 °C

0.0±1.2 mmHg at 25°C

1.628

3.73

1

3

6

21

312

1

CNCC[C@H](OC1=CC=CC2=C1C=CC=C2)C3=CC=CS3

ZEUITGRIYCTCEM-KRWDZBQOSA-N

InChI=1S/C18H19NOS/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16/h2-10,13,17,19H,11-12H2,1H3/t17-/m0/s1

(3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine

LY248686; LY-227942; LY-248686; LY 227942; (S)-Duloxetine; (S)-Duloxetine; Yentreve; Cymbalta; (S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine; LY 248686; HSDB 7368; Duloxetine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)