What is Atomoxetine?

Atomoxetine, also known as atomoxetine, is a chemical. Chemical name (-)- N -methyl-3-phenyl-3- ( o -tolyloxy) -propylamine, the molecular formula is C ₁₇ H ₂₁ NO, and the molecular weight is 255.35500. Tomoxetine is a drug for the nervous system and is mainly used in the treatment of attention deficit disorder (ADHD).

Drug Name: Tomoxetine
Foreign name: Atomoxetine

CAS number: 83015-26-3
Molecular formula: C17H21NO
Molecular weight: 255.35500

Tomoxetine Basic Information

Chinese name: tomoxetine

Chinese alias: ( R ) -N-methyl-3- (2-methylphenoxy) amphetamine

English name: atomoxetine

English alias: Astemizol; 1- (4-fluorophenylmethyl)-N-{1- [2- (4-methoxyphenyl) ethyl] -4-piperidinyl} -1 H -benzimidazol-2-amine; Histaminos; Hismanal; Laridal;

CAS number: 83015-26-3

Molecular formula: C ₁₇ H ₂₁ NO

Chemical structure:

Molecular weight: 255.35500

Exact mass: 255.16200

PSA: 21.26000

LogP: 4.33020 ^[1]

Tomoxetine physical and chemical properties

Density: 1.023g / cm ³

Boiling point: 389ºC at 760 mmHg

Flash point: 164.1ºC

Refractive index: 1.552

Flash point: 164.1 ° C

Vapor pressure: 2.95E-06mmHg at 25 ° C ^[2]

Tomoxetine Tomoxetine related drug label information

1 Tomoxetine 1, classification

Neurological Drugs> Antipsychotics, Antidepressants, Anxiolytics> Other

2 Tomoxetine 2, dosage form

5mg / cap; 10mg / cap; 18mg / cap; 25mg / cap; 40mg / cap; 60mg / cap (in terms of tomoxetine). Store in a dry and dark place at room temperature.

3 Tomoxetine 3, pharmacological effects of Tomoxetine

The exact mechanism of action of tomoxetine is unknown. Attention deficit disorder (ADHD in children), the pathogenesis is currently thought to be related to the reduction of the catecholamine neurotransmitter dopamine and norepinephrine adrenaline flipping effects. Tomoxetine can selectively inhibit the presynaptic function of norepinephrine, enhance the function of norepinephrine, thereby improving the symptoms of ADHD, indirectly promoting cognitive completion and concentration . Has little affinity for other neurotransmitter receptors such as cholinergic, histamine, dopamine, serotonin, and alpha-adrenergic receptors.

4 Pharmacokinetics of Tomoxetine 4, Tomoxetine

Tomoxetine is rapidly absorbed after oral administration, and reaches the peak blood level about 1 to 2 hours after administration. The absolute bioavailability in the strong metabolizer (EM) and weak metabolizer (PM) is about 63% and 94%, respectively. Food does not affect the absolute bioavailability of tomoxetine, but it can reduce its absorption rate, reduce the peak concentration (Cmax) by about 37%, and delay the peak time (Tmax) by about 3h. At the therapeutic dose of tomoxetine, the plasma protein binding rate is about 98%, which mainly binds to serum albumin; the apparent volume of distribution is 0.85L / kg, indicating that it is mainly distributed in body fluids. Tomoxetine is first metabolized by hepatic microsomal cytochrome P450 (CYP2D6) to produce 4-hydroxytomoxetine hydrochloride. The product formed is further combined with glucuronic acid. Similar to the original drug, the blood concentration is about 1% of the original drug. For adult EM and PM, the mean half-life of tomoxetine was 5.2h and 21.6h, respectively. The area under the medicine time curve (AUC) of PM is about 10 times that of EM. Tomoxetine is excreted mainly in urine in the form of 4-hydroxytomoxetine-O-glucuronide (> 80%), a small amount is excreted in feces (<17%), and a small amount is excreted in the original drug (<3% ). The pharmacokinetics of tomoxetine in children and adolescents over 6 years is similar to that in adults.

5 Indications for Tomoxetine 5, Tomoxetine

Tomoxetine is suitable for the treatment of attention deficit disorder (ADHD).

6 Tomoxetine 6, contraindications for tomoxetine

1). Those who are allergic to tomoxetine or other components are prohibited.

2). Patients with angle-closure glaucoma are disabled.

3). Disable pregnant women.

4). Patients who are taking or have taken monoamine oxidase inhibitors (such as phenylethylhydrazine, etc.) within the first 14 days are prohibited.

5). Tomoxetine can increase the risk of liver toxicity, and it is contraindicated in patients with acute liver failure.

7 Tomoxetine 7, precautions

1). Tomoxetine should not be used in combination with monoamine oxidase inhibitor (MAOI), and it can be used after 2 weeks of MAOI discontinuation.

2). The dose of tomoxetine should be adjusted when combined with CYP2D6 inhibitors such as fluoxetine, paroxetine or quinidine.

3). It can increase the risk of liver toxicity. Use with caution in patients with liver disease. Moderate and severe liver dysfunction and those with CYP2D6 metabolic enzyme deficiency should be reduced as appropriate.

4). The safety and efficacy of tomoxetine in children under the age and elderly patients have not yet been determined.

5) Tomoxetine can increase blood pressure and heart rate, and be used with caution in patients with hypertension, tachycardia, cardiovascular or cerebrovascular disease. Tomoxetine can also cause orthostatic hypotension, with caution in patients with or with a tendency to hypotension.

6) Use with caution when using salbutamol or other 2 receptor agonists.

7) Tomoxetine should be used with caution in lactating women.

8) Use with caution for those with weak metabolic capacity and those with a history of drug dependence.

9) Tomoxetine can cause urinary retention, with caution in patients with urinary retention or abnormal renal function.

8 Tomoxetine 8, adverse reactions to tomoxetine

Tomoxetine can cause severe liver damage, itchy skin, jaundice, dark urine, right upper abdominal tenderness, and influenza-like symptoms.

9 Tomoxetine 9

For children and adolescents weighing less than 70 kg, the initial dose of tomoxetine is about 0.5 mg / kg daily. It takes at least 3 days to increase the target dose to about 1.2 mg / kg daily. For ophthalmic use in the morning and afternoon / evening. The maximum daily dose does not exceed 1.4 mg / kg or 100 mg. For children, adolescents, and adults weighing 70 kg or more, the initial dose of tomoxetine is about 40 mg daily, and it can be increased to a target dose of about 80 mg daily after a minimum of 3 days. Take 2 times in the afternoon / evening. If the effect is not obvious, the maximum daily dose can be increased to 100 mg after 2 to 4 weeks of administration. Tomoxetine can be taken alone or with food. For patients with moderate liver damage, the dose is reduced to 50% of the normal dose, and for severe liver dysfunction, the dose is reduced to 25% of the normal dose.

10 Interaction of tomoxetine 10, tomoxetine and other drugs

1). Tomoxetine is mainly metabolized by liver CYP2D6. The CYP2D6 inhibitors paroxetine, fluoxetine, and quinidine can increase the steady-state plasma drug concentration of tomoxetine.

2). Combined with salbutamol, the adverse reactions of increased albuterol heart rate and increased blood pressure are aggravated.

3). The combination of tomoxetine and dexipramine did not change the pharmacokinetics of dexipramine.

4). Tomoxetine does not increase the incidence of methylphenidate cardiac events.

5). When combined with drugs with a high plasma protein binding rate, tomoxetine has no effect on the plasma protein binding rates of warfarin, aspirin, phenytoin, and diazepam.

6). Antacids increase gastric juice pH and have no effect on the bioavailability of tomoxetine. ^[3]