How Effective Is Ondansetron for Nausea?

Ondansetron, whose chemical name is 2,3-dihydro-9-methyl-3-[(2-methylimidazol-1-yl) methyl] -4 (1H) -carbazolone, is white Or off-white crystalline powder; odorless and bitter. Soluble in methanol, goose down in water, slightly soluble in acetone; slightly soluble in 0.1ml / L hydrochloric acid solution. The melting point is 175-180 ° C, and it decomposes at the same time when melting. It is clinically used to prevent or treat chemotherapy drugs (such as cisplatin, doxorubicin, etc.) and radiation therapy for nausea and vomiting.

Chinese name: Ondanstron
Foreign name: Ondansetro

CAS number: 99614-02-5
Molecular formula: C18H19N3O

Ondansetron compounds

Basic information

Chinese name

Chinese alias: Ondansetron; Ondansetron;

English name: Ondansetro;

English alias: 9-Methyl-3-((2-methyl-1H-imidazol-1-yl) methyl) -2,3-dihydro-1H-carbazol-4 (9H) -one; Ondansetron; ONDANSETRONBASE; 9-METHYL -3-[(2-METHYL-1H-IMIDAZOLYL) -METHYL] -1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; ONDANSETRON HYDROCHLORIDE DIHYDRATE; ONDANESTRON; ONDANSETRON HCL D6; ONDANSETRON HCL; R ( +)-Ondansetron; ONDANSETRON HYDROCHLORIDE; 9-METHYL-3-[(2-METHYL-1H-IMIDAZOLYL) METHYL] -1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; 9-METHYL-3 -(2-METHYL-1H-IMIDAZOLYL) -METHYL-1,2,3,9-TETRAHYDRO-4H-CARBAZOLE-4-ONE; ONDANSETRON FOR LC SYSTEM SUITABILITY, EP STANDARD; ONDANSETRON-D5;

CAS number: 99614-02-5

MDL number: MFCD00374371

RTECS number: FE6375500

Molecular formula: C ₁₈ H ₁₉ N ₃ O

Structural formula:

Molecular weight: 293.36300

Exact mass: 293.15300

PSA: 39.82000

LogP: 3.12850

Ondansetron physical and chemical properties

Appearance and properties: white to yellow crystal

Density: 1.27 g / cm ³

Melting point: 231-232ºC

Boiling point: 546ºC at 760 mmHg

Flash point: 284ºC

Refractive index: 1.691

Storage conditions: -20ºC

Ondan Setron Safety Information

Customs code: 2933990090

Dangerous Goods Transport Code: UN 2811 6.1 / PG 3

WGK Germany: 3

Danger category code: R25

Safety instructions: S45

RTECS number: FE6375500

Dangerous goods mark: T; Xi ^[1]

Ondansetron molecular structure data

1. Molar refractive index: 86.75

2. Molar volume (cm / mol): 230.1

3. Isotonic specific volume (90.2K): 608.7

4. Surface tension (dyne / cm): 48.9

5. Polarizability (10-24cm3): 34.39 ^[2]

Ondansetron synthesis method

2-bromoaniline reacts with 1,3-cyclohexanedione, and then dehydrobromide cyclizes to form a tetrahydrocarbazole derivative. The derivative reacts with dimethylamine and paraformaldehyde, and then reacts with methyl iodide. Finally, it was stirred with 2-methyl-1H-imidazole in dimethylformamide to obtain ondansetron.

Alternatively, cyclohexanone and phenylhydrazine can be reacted to obtain tetrahydrocarbazole. This was dissolved in tetrahydrofuran and water, and a tetrahydrofuran solution of 2,3,5,6-tetrachloro-1,4-benzoquinone was added dropwise under nitrogen, and the oxidation product was obtained by stirring. The product was refluxed with ethanol, concentrated hydrochloric acid, paraformaldehyde, and dimethylamine hydrochloride. After the treatment, concentrated hydrochloric acid was added in acetone and stirred, and the obtained aminomethylated product was reacted with 2-methylimidazole; then, it was stirred with methyl iodide and potassium carbonate at room temperature until the solid disappeared. After processing, Ondansetron was obtained. It is dissolved in a mixed solution of acetone and water and reacted by adding concentrated hydrochloric acid to obtain ondansetron hydrochloride dihydrate.

It can also be reacted with 1,2,3,9-tetraoxy-4H-carbazol-4-one with dimethylamine and paraformaldehyde, and then with methyl iodide, and finally with 2-methyl-1H-imidazole in Reaction in dimethylformamide to give ondansetron. ^[2]

Ondansetron uses

This product is a highly selective serotonin (5-HT3) receptor antagonist, which can inhibit nausea and vomiting caused by chemotherapy and radiotherapy, has high intensity and high selectivity, can control the receptors in the small intestine and CTZ Vomiting due to irritation. It is suitable for the treatment of nausea and vomiting caused by chemotherapy and radiotherapy. It can also be used to prevent and treat nausea and vomiting caused by surgery. ^[2]

Ondansetron pharmacological effects

Ondansetron is a powerful and highly selective serotonin 3 (5-HT3) receptor antagonist, which can effectively inhibit or alleviate nausea and vomiting caused by cytotoxic chemotherapy drugs and radiotherapy, and its efficacy is better than metoclopr Clopromide; It has a rapid and powerful inhibitory effect on vomiting caused by some strong vomiting chemotherapeutic drugs (such as cisplatin, cyclophosphamide, doxorubicin, etc.), but it has vomiting caused by motion sickness and apomorphine invalid. The exact mechanism of action of Ondansetron is not completely clear. It is generally believed that chemotherapy and radiotherapy can cause serotonin (5-HT) to be released from chromaffin cells in the small intestine, and cause vagal afferent nerve excitement through the 5-HT3 receptor, leading to vomiting reflex, and ondansetron can block this reflex happened. This effect is 100 times stronger than the traditional antiemetic drug metoclopramide. Excitation of the vagus afferent nerve can also cause the release of 5-HT in the posterior branch of the fourth ventricle, which can also trigger vomiting through a central mechanism. Therefore, the mechanism of ondansetron to control nausea and vomiting caused by cytotoxic chemotherapeutics and radiation therapy may be due to antagonistic 5-HT3 receptors in the periphery and central. The mechanism of action of ondansetron for nausea and vomiting after surgery is unknown. At the same time, ondansetron can also increase gastric emptying at an antiemetic dose, which helps reduce nausea; it also has anti-anxiety and diazepam effects on the central nervous system, which is conducive to suppressing the excitement of the vomiting center. ^[3]

Ondansetron pharmacokinetics

Ondansetron is rapidly absorbed orally and has a bioavailability of approximately 60%. After a single oral administration of 8 mg, the blood concentration reached a peak value (30 ng / ml) in 1.5 h. It is quickly distributed to all tissues of the body after oral administration. The plasma protein binding rate is 70% to 76%, the apparent volume of distribution (Vd) is 140L, and it can be secreted by milk. The metabolism of the drug by oral administration is similar to that of intravenous injection. It is mainly metabolized by the liver. The half-life phase is about 3 hours. Metabolites are mainly excreted from feces and urine, and less than 50% of them are excreted from the urine in their original form. Repeated administration does not change its pharmacokinetics. ^[3]

Ondansetron indications

1. For the prevention and treatment of nausea and vomiting caused by chemotherapy and radiotherapy, especially the anti-cancer drug cisplatin has a significant effect.

2. There are reports in the literature that can also be used to prevent and treat nausea and vomiting after surgery. ^[3]

Ondansetron contraindications

1. People with allergies or allergies to Ondansetron.

2. Patients with gastrointestinal obstruction.

3. Banned for pregnant women and lactating women. ^[3]

Ondansetron dosage forms and specifications

1. Injection: 4mg (2ml), 8mg (4ml);

2. Tablet or capsule: 4mg, 8mg. ^[3]

Ondansetron Dosage

1. (1) Treatment of nausea and vomiting caused by chemotherapy and radiotherapy: For chemotherapy and radiotherapy that can cause moderate vomiting, 8 mg should be taken orally 1 to 2 hours before treatment and 8 mg after 12 hours. In order to avoid nausea and vomiting 24h after treatment, patients should continue to take medicine, 8mg each time, twice a day for 5 days. (2) Prevention or treatment of vomiting after surgery: 8 mg orally 1 hour before anesthesia, and 8 mg orally every 8 hours thereafter, a total of 2 times.

2. Intravenous injection: When treating nausea and vomiting caused by chemotherapy and radiotherapy, chemotherapy and radiotherapy that can cause moderate vomiting should be slowly injected intravenously 8mg before the patient receives treatment; for chemotherapy and radiotherapy that can cause severe vomiting, 8 mg of Ondansetron was given slowly before treatment, and then 8 mg was given slowly at intervals of 2 to 4 hours, a total of 2 times. In the above two cases, in order to avoid nausea and vomiting after 24 hours of treatment, patients should continue to take medication, 8 mg each time, twice a day for 5 days.

3. Intravenous infusion: (1) Treatment of severe vomiting caused by chemotherapy and radiotherapy: Ondansetron is added to 50-100 ml of normal saline intravenously before chemotherapy, and the infusion time is 15 minutes. For chemotherapy that may cause severe vomiting, ondansetron and 20 mg of dexamethasone sodium phosphate may be administered by intravenous infusion before treatment to enhance the efficacy of ondansetron. In order to avoid nausea and vomiting 24 hours after treatment, patients should continue to take medication, 8 mg each time, twice a day for 5 days. (2) Prevention of postoperative vomiting: Generally, 4 mg can be administered intravenously before induction of anesthesia. (3) Treatment of vomiting after surgery: Slowly inject 4mg for treatment. ^[3]

Ondansetron adverse reactions

1. Liver function damage: Because Ondansetron is metabolized by the liver, the daily dosage of moderate and high liver dysfunction and the elderly and infirm should not exceed 0.15mg / kg. At the same time, hepatoprotective should be used when liver function deteriorates drug.

2. Dry stool and bloating: due to Ondansetron's inhibition of intestinal peristalsis, severe symptoms can last 5 to 7 days. It is not difficult to deal with such situations. Pay attention to adjusting the diet structure, increasing exercise, and appropriately cooperating with internal medicines such as gastrointestinal motility drugs. Generally, it can also relieve itself.

3. Rash: skin rash, rash, or transient redness in the skin around the injection.

4. Headaches, dizziness, tachycardia, and chest discomfort are rare. They are transient and do not require treatment or symptomatic treatment. Sedentary inability, bronchospasm, diarrhea, major epilepsy, hypokalemia, etc. are occasional.

5. Some patients may have transient asymptomatic elevation of aminotransferase.

6. There have been reports of immediate allergic reactions. ^[3]

Ondan Sejong notes

1. Use with caution for allergies.

2. Children, the elderly and pregnant women are not strictly contraindicated, but should not be controlled in excess per day, and should be 0.15mg / kg. The safety of ondansetron for human pregnancy has not been established, and the use of ondansetron during early pregnancy is not recommended.

3. The elimination half-life of the elderly and those with poor liver function can be extended to 5h or longer, and the dose should be controlled.

4. For patients with kidney damage, there is no need to adjust the dosage, the number of times of medication and the way of use.

5. The incidence of adverse reactions will increase when the drug is overdose.

6. Ondansetron should be protected from light below 30 ° C.

7. Intravenous injection speed must be slow. ^[3]

Ondansetron interactions with other drugs

1. Combined with dexamethasone or metoclopramide to achieve better results.

2. Ondansetron is metabolized by the liver P450 enzyme system. Therefore, anything that can induce or inhibit the enzyme system may change its clearance rate and thus change its half-life. However, there is not enough information on how to adjust or it is necessary to adjust the dose.

3. In humans, carmustine, etoposide and cisplatin do not affect the metabolism of ondansetron. ^[3]

Ondan Sejong expert reviews

1. Ondansetron is a potent and highly selective serotonin 3 (5-HT3) receptor antagonist. Chemotherapy drugs and palliative treatments can cause serotonin release in the small intestine, and the vagus afferent nerve excitement through the (5-HT3) receptor causes vomiting reflex. Ondansetron can block this reflex. This prevents nausea and vomiting caused by chemotherapy and radiotherapy. The effect is better than metoclopramide. It has the effect of promoting gastric motility and accelerating gastric emptying, which is beneficial to antiemetic.

2. Ondansetron alone is about 90% effective, and 69% to 85% effective for large doses of cisplatin. It is safe and effective, and is currently the first choice for clinical use.

3. Phase I clinical trials were observed at different doses of 0.01 to 0.48 mg / kg × 3 times (within 24 hours), and the curative effect was found to be in parallel with the dose. However, when the dose was as high as 0.48 mg / kg, adverse reactions increased significantly. Currently, It was agreed that the optimal dose at one time was 0.15 mg / kg.

4. Practice has proven that the antiemetic effect of Ondansetron administered every 2, 4, 6, 8 or 12 hours is the same, so once a day is sufficient. In order to achieve the largest and lasting antiemetic effect, it is not necessary to keep the blood concentration at a high level all the time. In the past, the report that Ondansetron was required to be used in large doses (24 mg or 32 mg) several times a day has been basically abandoned.

5. It turns out that Ondansetron is the same as other 5-HT3 antagonists in that its antiemetic effect is better than traditional antiemetics. It is the control of acute reactions, and the treatment of delayed reactions is similar to traditional Like antiemetics, there is no advantage.

6. Although the antiemetic effect of Ondansetron has been affirmed, 9% to 30% of cases are not enough to completely stop vomiting when used alone. It was clinically found that these cases had no obvious relationship with the use, dosage, and duration of the drug. It is speculated that these cases may have another vomiting mechanism or pathway. Is it an individual difference or the 5-HT3 receptor is blocked, other receptors are still Works. Based on this, when encountering such problems, you should avoid increasing the dose of the drug or replacing one 5-HT3 receptor antagonist with another 5-HT3 receptor antagonist. You should consider a variety of antiemetic mechanisms. Drugs are used in combination, rather than a combination of many different types of 5-HT3 receptor antagonists. This can improve the antiemetic effect without increasing side effects.

7. There is no difference in the antiemetic effect of tablets (or capsules) and injections of the same dosage, and their adverse reactions are similar. They can be selected as appropriate in clinical situations. ^[3]