What Is Paroxetine?

Paroxetine, is used to treat depression. It is suitable for the treatment of depression patients with anxiety. Its effect is faster than TCAs, and its long-term effect is better than imipramine. It can also be used for the treatment of original terror disorder, social phobia and obsessive-compulsive disorder.

Drug type: Essential medicines
Drug name: Paroxetine

English name: Paroxetine
Chinese alias: Droperifen
English alias: Paxil; Seroxat

Paroxetine chemical name

(A)-(3S 4S) -4- (4-fluorophenyl) -3-[[(3 4-Methyleneoxy) phenoxy] methyl] piperidine

Molecular formula of paroxetine

Paroxetine molecular formula

C19H20FN03

Paroxetine molecular weight

374

Physicochemical properties of paroxetine

Its hydrochloride or mesylate is commonly used. Hydrochloride is white or off-white, easily deliquescence crystalline powder, easily soluble in methanol, slightly soluble in absolute ethanol and dichloromethane, slightly soluble in water. Methanesulfonate is an off-white powder, odorless, solubility in water is> lg / ml, melting point is 147 ~ 150 .

Paroxetine Pharmacology

This product is a phenylpiperidine derivative and SSRI, which can selectively inhibit the 5-HT transporter, block the reuptake of 5-HT by the presynaptic membrane, and prolong and increase the effect of 5-HT, thus Produces antidepressant effects. At commonly used doses, it had no significant effect on other transmitters except for the weak inhibition of NA and DA reuptake. It can be completely absorbed after oral administration, and its bioavailability is 50%. Neither food nor drugs will affect its absorption. There is a first pass effect. The plasma half-life is 24 hours, and the half-life of the elderly will be prolonged. The plasma protein binding rate was 95%. Can be distributed in all tissues and organs of the body, can also be secreted through the breast. It is mainly metabolized by the liver to produce uridine compounds, some of which are mediated by CYP2D6. Finally it is excreted by the kidneys, and a small part is excreted from the feces by bile secretion.

Paroxetine indications

Used to treat depression. It is suitable for the treatment of depression patients with anxiety. Its effect is faster than TCAs, and its long-term effect is better than imipramine. It can also be used for the treatment of original terror disorder, social phobia and obsessive-compulsive disorder.

Paroxetine usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Paroxetine adverse reactions

Slight and short. Common symptoms include mild dry mouth, nausea, anorexia, constipation, headache, tremor, fatigue, insomnia, and sexual dysfunction. Occasional neuroedema, urticaria, orthostatic hypotension. Rare reports of extrapyramidal reactions.

Paroxetine contraindications

Those who are allergic to this product are prohibited. Not suitable for pregnant and lactating women.

Paroxetine precautions

See Fluoxetine. MA0Is cannot be used within two weeks before and after taking this medicine. Patients with a history of epilepsy or mania, angle-closure glaucoma, bleeding tendency, suicidal tendency or history of severe depression should be used with caution. Liver and kidney dysfunction can still be used safely, but the dose should be reduced. After one-time administration, slight heart rate slowdown and blood pressure fluctuations may occur, which are generally not clinically significant, but for patients with cardiovascular disease or newly discovered myocardial infarction, attention should be paid to their response. Effective after taking 1-3 weeks. Long enough to consolidate the effect. The duration of maintenance treatment for depression, obsessive-compulsive disorder, and panic disorder is longer. It is reported that rapid withdrawal can cause syndromes: sleep disturbance, irritability or anxiety, nausea, sweating, and confusion. In order to avoid the withdrawal reaction, the withdrawal plan is recommended: according to the patient's tolerance, if it can be tolerated, reduce the rate at a rate of 10 mg per week to a daily dose of 20 mg should be maintained orally for 1 week before discontinuation. If the tolerance is not tolerated, the reduced dose may be reduced. If the patient responds strongly, the original dose may be considered.

Paroxetine drug interactions

SSRIs are not allowed to be combined with MA0Is drugs. Prohibit the use of another drug within 4 days of discontinuation of SSRIs or MA0fel. Otherwise, it may cause 5-HT syndrome (clinical manifestations of fever, muscle rigidity, myoclonus, mental symptoms, and even changes in vital signs). Combination with other 5-HT active drugs (lithium salt, tryptophan, tramadol, triptans, St. John's wort, or other SSRIs, SNRIs, and TCAs) may increase and lead to 5-HT energy nerve activity Hyperthyroidism occurs with 5-HT syndrome. Combined with cisapride, thioridazine, pimochet, and terfenadine, it will cause cardiac toxicity, lead to prolonged QT interval, and cardiac arrest. Should not be combined. Inhibitors or substrates with CYP2D6 or other CYP isoenzymes (such as cimetidine, amitriptyline, clozacarb, perphenazine, maprotiline, imipramine, ritonavir, (Buspirone, alprazolam, etc.) can increase the blood concentration of this product. Combination with CYP inducer (such as carbamazepine, phenobarbital, phenytoin, etc.) will reduce the blood concentration and efficacy of this product. Combined with hypoglycemic drugs, can lower blood sugar and even cause hypoglycemia. Glucose rises when this product is stopped. Therefore, after using this product and stopping the drug for a period of time, blood glucose levels should be monitored and timely intervention measures should be taken. SSRIS, 5-HT, and NE dual reuptake inhibitors (SNRIs) all increase the risk of bleeding, especially when combined with aspirin, warfarin, and other anticoagulants. The combination of radon and digoxin may increase its blood concentration and increase the risk of digitalis poisoning.

Paroxetine

Tablet: 20mg

Introduction to Paroxetine Pharmacopeia

[Identification] (1) Take this product, add methanol to dissolve and make a solution containing 5 (Vg per 1ml), and measure according to ultraviolet-visible spectrophotometry (Appendix IV A), at the wavelengths of 235nm, 265nm, 271nm and 295nm Has the maximum absorption. The ratio of the absorbance at the wavelength of 235nm to the absorbance at the wavelength of 295nm should be 0.92-0.96. (2) The chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be the main peak of the reference solution The retention time is the same. (3) The infrared absorption spectrum of this product should be consistent with that of the reference product (Appendix IV C). (4) This product shows the identification reaction of organic fluoride (Appendix III). (5) This product The aqueous solution shows the identification reaction of chlorides (Appendix III). [Check] For acidity, take 0.10g of this product, add 10ml of water, heat to dissolve, let cool, and measure according to law (Appendix VI H). The pH value should be 5.5 6.5. Take this product from the structure, weigh it accurately, add methanol to dissolve and quantitatively dilute to make a solution containing about 1mg per lml as the test solution; take 1ml precisely, place it in a 100ml volumetric flask, and dilute to the mark with methanol. Shake well as a control solution; take paroxetine hydrochloride and transpax An appropriate amount of the Xi Ting reference substance was dissolved and diluted with methanol to prepare a mixed solution containing 0.1 mg per 1 ml as a system suitability test solution. As determined by high performance liquid chromatography (Appendix VD), -acid glycoprotein was used. Bonded silica gel as filler (100mmX4.0mm, 5µm), dipotassium hydrogen phosphate buffer solution (take 11.4 g of dipotassium hydrogen phosphate, add 1000 ml of water to dissolve, adjust pH to 6.5 with phosphoric acid)-acetonitrile (94: 6) It is a mobile phase with a detection wavelength of 295nm and a column temperature of 30 ° C. Measure 10 l of the system suitability test solution and inject it into the liquid chromatograph to adjust the detection sensitivity so that the peak height of the paroxetine hydrochloride peak is about 90% of the full scale. The number of theoretical plates is not less than 200 based on the paroxetine hydrochloride peak, and the resolution of the paroxetine hydrochloride peak and the trans paroxetine peak should be greater than 2.2. Then accurately measure 10 l of the test solution and the control solution, and inject them into the liquid phase. Chromatograph, record the chromatogram. If there is a trans-paroxetine peak in the chromatogram of the test solution, the peak area should not be greater than 0.1 times (0.1%) of the main peak area of the control solution. Take this product and add the solvent [tetrahydrofuran- Water (1: 9)] dissolved and Release into a solution containing about 1mg per 1ml as the test solution. Take a precise amount and dilute it quantitatively with a solvent to make a solution containing about 1µg per 1ml as a control solution. Take paroxetine hydrochloride and deflupaparine Roxetine and N-methylparoxetine reference substance, dissolved in solvent and diluted to make a mixed solution containing 10 µg per 1 ml, as a system suitability test solution. Tested according to high performance liquid chromatography (Appendix VD), using octyl Silconium bonded silica gel is used as a filler, and trifluoroacetic acid-tetrahydrofuran-water (5: 100: 900) is used as mobile phase A, and trifluoroacetic acid-tetrahydrofuran-acetonitrile (5: 100: 900) is used as mobile phase B. Press The table was subjected to gradient elution with a detection wavelength of 295 nm.

yansuanpalu0xiting.jpg Take 20µ1 of the system suitability test solution, inject it into the liquid chromatograph, record the chromatogram, and the peak order is defluoxetoxetine, N-methyl paroxetine, and paroxetine hydrochloride. Not less than 6000, the resolution between the paroxetine hydrochloride peak, defluoxetoxetine peak and N-methyl paroxetine peak should be greater than 2.5. Precisely measure 20µl of the control solution, and inject it into the liquid chromatograph. Adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 10% of the full range. Then accurately measure 20µl of the test solution and the control solution, and inject the solution separately. Phase chromatograph, record chromatogram. If there is an impurity peak in the chromatogram of the test solution that has the same retention time as the defluparoxetine peak, its peak area must not be greater than the area of the main peak of the control solution (0.1%). ), The sum of the peak areas of each impurity must not be greater than 5 times (0.5%) the main peak area of the control solution. Any impurity peak in the test solution that is less than 0.5 times the area of the main peak of the control solution can be ignored. Residual solvents: methanol, ethanol, acetone, tetragas furan, pyridine and toluene. Take about 2.0g of this product, weigh it accurately, place it in a 20ml volumetric flask, and add the internal standard solution precisely (take an appropriate amount of n-propanol, use dimethylsulfoxide). Make a solution containing about 5 mg per 1 ml) 2 ml, dilute to the mark with dimethyl sulfoxide, shake well, and use it as a test solution. Accurately weigh the appropriate amount of methanol, ethanol, acetone, tetrahydrofuran, pyridine and toluene, and use dimethyl sulfoxide to make a solution containing 3mg, 5mg, 5mg, 0.72mg, 0.2mg and 0.89mg per 1ml, and store it as a reference. Solution: Precisely measure 5ml each of the reference solution and the internal standard solution, place them in a 50ml volumetric flask, dilute to the mark with dimethyl sulfoxide, shake well, and use it as the reference solution. Precisely measure 10ml each of the reference solution and the test solution, place them in the headspace bottle, and seal. According to the residual solvent determination method (Appendix P second method) test, 6% cyanopropylphenyl-94% dimethyl polysiloxane (or similar polarity) as the fixed solution, the starting temperature is 50 , Maintain for 10 minutes, heat up to 80 ° C at a rate of 6 ° C per minute, maintain it for 5 minutes, and then raise it to 150 ° C at a rate of 40 ° C per minute for 5 minutes. The equilibrium temperature of the headspace bottle is 90 ° C and the equilibrium time is 30. minute. Take the reference solution headspace sample and record the chromatogram. The number of theoretical plates calculated from the n-propanol peak is not less than 10,000, and the resolution between the peaks of each component should meet the requirements. Then take the test solution and reference solution for headspace injection, record the chromatogram, and calculate the peak area according to the internal standard method, which should meet the requirements. Moisture is taken from this product and measured according to the Moisture Measurement Method (Appendix WM, First Method A). The moisture content is 2.0% to 3.0%. Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. The heavy metal shall be taken as the residue left under the item of burning residue, and shall be inspected according to law (Appendix VI H second method). The content of heavy metal shall not exceed 10 parts per million. [Content determination] Determination according to high performance liquid chromatography (Appendix VD). Chromatographic conditions and system suitability tests use octadecylsilane bonded silica as a filler; take 3.96g of ammonium acetate, add 720ml of water to dissolve, add 280ml of acetonitrile, 10rnl of triethylamine, adjust the pH to 5.5 with glacial acetic acid for flow Phase; detection wavelength is 295nm. Take 5mg each of paroxetine hydrochloride, defluparoxetine and N-methylparoxetine reference substance, put them in the same 10ml volumetric flask, add mobile phase to dissolve and dilute to the mark, shake well, as the system suitability test solution, Take 20µl into the liquid chromatograph and record the chromatogram. The order of the peaks is defluoxetine, paroxetine hydrochloride, N-methyl paroxetine peak. The theoretical number of plates is not less than 3000 calculated from paroxetine hydrochloride peak. The resolution between the paroxetine peak, the defluoxet paroxetine peak and the N-methyl paroxetine peak should all meet the requirements. About 10mg of this product is determined by measurement. Weigh it accurately, put it in a 100ml measuring flask, add mobile phase to dissolve and dilute to the mark, shake well, and accurately measure 20µ1 into the liquid chromatograph and record the chromatogram. Another paroxetine hydrochloride control The product is determined by the same method, and the peak area is calculated according to the external standard method. [Category] Antidepressants. [Storage] Keep sealed.

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