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Ondansetron
ONDANSETRON HCL · ONDANSETRON HYDROCHLORIDE DIHYDRATE · ONDANSETRON HCL DIHYDRATE · Ondansetro · Ondanestron · ONDANCETRON · 1,2,3,4-Tetrahydro-9-methyl-3-(2-methyl-1H-imidazol-1-ylmethyl)carbazol-4-one · Yatrox
Identifikatoren & physikalische Daten
| CAS No. | 99614-02-5 |
|---|---|
| Summenformel | C18H19N3O |
| Durchschnittliche Molmasse | 293,4 g/mol |
| Monoisotopische Masse | 293,15281223 g/mol |
| SMILES | Cc1nccn1CC1CCc2c(c3ccccc3n2C)C1=O |
| InChIKey | FELGMEQIXOGIFQ-UHFFFAOYSA-N |
| PubChem CID | 4595 |
| ChEMBL | CHEMBL46 |
| ChEBI | CHEBI:7773 |
| EC No. | 619-449-4 |
| DTXSID | DTXSID8023393 |
Chemische & physikalische Eigenschaften
| XLogP | 2,3 |
|---|---|
| Polarare Oberfläche (TPSA) | 39,8 |
| H-Brücken-Donoren | 0 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 22 |
| Formalladung | 0 |
| Komplexität | 440 |
| Arzneimittel | Pharmaceuticals |
| LogP (Verteilungskoeffizient) | 1.92 |
| Color/Form | Crystals from methanol |
| Löslichkeit | Sparingly soluble in waterVery soluble in acid solutionsH2O: >5 mg/mL |
| Human Drugs | Breast FeedingLactationMilk, HumanAntiemeticsGastrointestinal AgentsSerotonin AntagonistsSerotonin 5-HT3 Receptor AntagonistsFDA approved drugs -> Active ingredientAntiemetic medicines |
| Schmelzpunkt | 231-232 °C231 - 232 °C231-232° |
| Physical Description | Solid |
| Stability/Shelf Life | Stable under recommended storage conditions. /Ondansetron hydrochloride dihydrate/ |
| Collision Cross Section | 171.7 Ų [M+H]+ [CCS Type: TWMethod: Major Mix IMS/Tof Calibration Kit (Waters)] |
| Other Experimental Properties | White crystalline solid from water/isopropanol. MP: 178.5-179.5 °C. pKa 7.4 /Ondanestron hydrochloride dihydrate/ |
| Siedepunkt | 435.21°C (rough estimate) |
| Dichte | 1.1385 (rough estimate) |
| Brechungsindex | 1.5855 (estimate) |
| Lagerbedingungen | −20°C |
| Aggregatzustand | solid |
| pKa (Säurekonstante) | pKa 7.4 (Uncertain) |
| Farbe | white |
| InChI | 1S/C18H19N3O/c1-12-19-9-10-21(12)11-13-7-8-16-17(18(13)22)14-5-3-4-6-15(14)20(16)2/h3-6,9-10,13H,7-8,11H2,1-2H3 |
| InChIKey | FELGMEQIXOGIFQ-UHFFFAOYSA-N |
| SMILES | [n]4(c(ncc4)C)CC1CCc2[n](c3c(c2C1=O)cccc3)C |
| CAS Datenbank | 99614-02-5(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (88.2%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P260, P261, P263, P264, P264+P265, P270, P271, P273, P280, P301+P316, P302+P352, P304+P340, P305+P351+P338, P305+P354+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 17 reports by companies from 9 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.H301: Toxic if swallowed [Danger Acute toxicity, oral] |
|---|---|
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ondansetron, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including ondansetron hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Ondansetron hydrochloride/ |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides, nitrogen oxides (NOx), Hydrogen chloride gas /Ondansetron hydrochloride dihydrate/ |
| Hazard Classes and Categories | Acute Tox. 3 (88.2%) |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents /Ondansetron hydrochloride dihydrate/ |
| Brandbekämpfungsverfahren | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. /Ondansetron hydrochloride dihydrate/Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. /Ondansetron hydrochloride dihydrate/ |
| Lagerbedingungen | Store upright between 15 deg and 30 °C (59 deg and 86 °F). Protect from light. Store bottles upright in cartons.Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: -20 °C. /Ondansetron hydrochloride dihydrate/ |
| Reinigungsverfahren | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Wear respiratory protection. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dustEnvironmental precautions: Prevent further leakage or spillage if safe to do so. Do not let product enter drainsMethods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. /Ondansetron hydrochloride dihydrate/ |
| Entsorgungsverfahren | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.Product: Offer surplus and non-recyclable solutions to a licensed disposal company. Contact a licensed professional waste disposal service to dispose of this material. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubberContaminated packaging: Dispose of as unused product. /Ondansetron hydrochloride dihydrate/ |
| Preventive Measures | Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Normal measures for preventive fire protection. /Ondansetron hydrochloride dihydrate/Appropriate engineering controls: Avoid contact with skin, eyes and clothing. Wash hands before breaks and immediately after handling the product. /Ondansetron hydrochloride dihydrate/Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Ondansetron hydrochloride dihydrate/SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
| Personal Protective Equipment (PPE) | Eye/face protection: Face shield and safety glasses. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Ondansetron hydrochloride dihydrate/Skin protection: Handle with gloves. /Ondansetron hydrochloride dihydrate/Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Ondansetron hydrochloride dihydrate/Respiratory protection: Where risk assessment shows air-purifying respirators are appropriate use a full-face particle respirator type N99 (US) or type P2 (EN 143) respirator cartridges as a backup to engineering controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Ondansetron hydrochloride dihydrate/ |
| Treatment | There is no specific antidote for ondansetron overdose. Patients should be managed with appropriate supportive therapy. (L1712) |
| Wechselwirkungen | The nephrotoxicity limits the clinical application of cisplatin. Human organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATEs) work in concert in the elimination of cationic drugs such as cisplatin from the kidney. We hypothesized that co-administration of ondansetron would have an effect on cisplatin nephrotoxicity by altering the function of cisplatin transporters. The inhibitory potencies of ondansetron on metformin accumulation mediated by OCT2 and MATEs were determined in the stable HEK-293 cells expressing these transporters. The effects of ondansetron on drug disposition in vivo were examined by conducting the pharmacokinetics of metformin, a classical substrate for OCTs and MATEs, in wild-type and Mate1-/- mice. The nephrotoxicity was assessed in the wild-type and Mate1-/- mice received cisplatin with and without ondansetron. Both MATEs, including human MATE1, human MATE2-K, and mouse Mate1, and OCT2 (human and mouse) were subject to ondansetron inhibition, with much greater potencies by ondansetron on MATEs. Ondansetron significantly increased tissue accumulation and pharmacokinetic exposure of metformin in wild-type but not in Mate1-/- mice. Moreover, ondansetron treatment significantly enhanced renal accumulation of cisplatin and cisplatin-induced nephrotoxicity which were indicated by increased levels of biochemical and molecular biomarkers and more severe pathohistological changes in mice. Similar increases in nephrotoxicity were caused by genetic deficiency of MATE function in mice. Therefore, the potent inhibition of MATEs by ondansetron enhances the nephrotoxicity associated with cisplatin treatment in mice. Potential nephrotoxic effects of combining the chemotherapeutic cisplatin and the antiemetic 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, such as ondansetron, should be investigated in patients.Although no pharmacokinetic drug interaction between ondansetron and tramadol has been observed, data from 2 small trials indicate that ondansetron may be associated with an increase in patient controlled administration of tramadol.Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular abnormalities) has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors.In patients treated with potent inducers of CYP3A4 (i.e., phenytoin, carbamazepine, and rifampicin), the clearance of ondansetron was significantly increased and ondansetron blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for ondansetron is recommended for patients on these drugs.For more Interactions (Complete) data for Ondansetron (8 total), please visit the HSDB record page. |
| Unerwünschte Wirkungen | The most commonly reported side effects (occurring in more than 10% of adults) include headaches, fatigue, dry mouth, malaise, and constipation. Some less common effects range from central nervous system (CNS) manifestations, such as drowsiness and sedation, to local injection site reactions and pruritus. A transient increase in liver function tests has also been reported. The pattern of liver enzyme elevation is normally hepatocellular, with rare cases of clinically apparent acute liver injury or jaundice. |
| Expositionspfade | Ondansetron is well absorbed after oral administration and undergoes limited first-pass metabolism. |
| Toxizitätsübersicht | IDENTIFICATION AND USE: Ondansetron forms as crystals from methanol. It is a drug used for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy in both human and veterinary cases. Prolongation of the QT interval and cases of torsades de pointes have been reported in patients receiving ondansetron. Liver failure and death have been reported rarely in patients with cancer receiving ondansetron concomitantly with other drugs, including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. Ondansetron hydrochloride may cause a serious anaphylactic reaction. In a study of children whose mothers received promethazine or ondansetron during pregnancy, no clinically significant adverse neurobehavioral effects or obstetric outcomes were identified. According to a different study, the teratogenic risk with ondansetron is low but an increased risk for a cardiac septum defect is likely. There was also no evidence of damage to genetic material noted in in vitro chromosome aberration tests using human peripheral lymphocytes. ANIMAL STUDIES: Ondansetron was administered orally to rats at doses of 1, 4, and 15 mg/kg during gametogenesis, mating, pregnancy, and lactation periods. It is proposed that the maximum noneffective dose of ondansetron was 4 and 15 mg/kg with respect to general toxicity and reproductive capacity in F0 animals respectively. The maximum noneffective dose with respect to development in F1 and F2 animals was suggested to be 15 mg/kg. After IV administration of 0.5, 1.5, and 4 mg/kg of ondansetron daily during gestation and lactation period, the results suggest that the maximum noneffective dose of ondansetron for general toxicity in dams was 1.5 mg/kg and that for reproduction toxicity in dams and developmental toxicity in fetuses and offspring was 4 mg/kg. A slight maternal toxicity was observed at the highest dose level in intravenous organogenesis (4.0 mg/kg/day) studies in the rabbit. Effects included maternal body weight loss and increased incidence of early fetal death. There was no evidence of damage to genetic material noted in in vitro V-79 mammalian cell mutation studies or in vivo chromosome aberration assays in mouse bone marrow. No evidence of mutagenicity was observed in microbial mutagen tests using mutant strains of Salmonella typhimurium, Escherichia coli or Saccharomyces cerevisiae, with or without a rat liver post-mitochondrial metabolizing system. Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 and 30 mg/kg/day, respectively.There is no known antidote to ondansetron, and supportive measures are used for overdose. A case report describes an ondansetron overdose in an infant presenting with seizures, QTc prolongation, hepatotoxicity, and serotonin syndrome. The patient required endotracheal intubation, supportive care, and lorazepam for seizures.Ondansetron is a selective serotonin 5-HT<sub>3</sub> receptor antagonist. The antiemetic activity of the drug is brought about through the inhibition of 5-HT<sub>3</sub> receptors present both centrally (medullary chemoreceptor zone) and peripherally (GI tract). This inhibition of 5-HT<sub>3</sub> receptors in turn inhibits the visceral afferent stimulation of the vomiting center, likely indirectly at the level of the area postrema, as well as through direct inhibition of serotonin activity within the area postrema and the chemoreceptor trigger zone. |
| Signs and Symptoms | Low blood pressure and fainting, sudden blindness, severe constipation |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of December 17, 2015: http://actor.epa.gov/dashboard/] |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Prolongation of the QT interval has been observed with ondansetron and other members of the 5-HT3 antagonist class. This /was a/ QTc study of ondansetron conducted in accordance with ICH E14 guidelines, designed to investigate the effect of single intravenous (IV) doses of ondansetron on cardiac conduction compared to placebo and a positive control, moxifloxacin, in healthy subjects. Statistical analysis of dose-response showed the maximum mean difference in QTcF, compared to placebo and corrected for baseline (ddQTcF), was less than 10 milliseconds (ms) after an 8 mg IV dose and approximately 20 ms after the 32 mg dose, each infused over 15 minutes. The concentration-response (Cp-ddQTcF) model resulted in similar predictions for the 8 and 32 mg and was used to predict the maximum mean ddQTcF (upper 90% CI bound) of 9.2 (11.2) ms for 16 mg IV. As a result, single IV doses of ondansetron greater than 16 mg should no longer be used. Adult cancer patients, under 75 years, may receive up to a maximum initial 15-minute IV dose of 16 mg, prior to chemotherapy, followed by 2 additional IV or IM doses of 8 mg for the management of chemotherapy-induced nausea and vomiting (CINV)./SIGNS AND SYMPTOMS/ Prolongation of the QT interval and cases of torsades de pointes have been reported in patients receiving ondansetron./SIGNS AND SYMPTOMS/ Individual doses of 84 mg and 145 mg and total daily doses as large as 252 mg have been administered with only mild side effects./SIGNS AND SYMPTOMS/ Liver failure and death have been reported rarely in patients with cancer receiving ondansetron concomitantly with other drugs, including potentially hepatotoxic cytotoxic chemotherapy and antibioticsthe etiology of the liver failure is unclear.For more Human Toxicity Excerpts (Complete) data for Ondansetron (14 total), please visit the HSDB record page. |
| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)ondansetronDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Carcinogenic effects were not seen in 2-year studies in rats and mice with oral ondansetron doses up to 10 and 30 mg/kg/day, respectively./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Ondansetron, a serotoninergic 5-HT3 receptor antagonist which can inhibit radiation- and cytotoxic substances-induced vomiting, was administered orally to rats at doses of 1, 4, and 15 mg/kg during gametogenesis, mating, pregnancy, and lactation periods. The body weight gain of F0 male and female during the premating period, pregnancy, and lactation, mating capacity of F0 animals, and development of F1 and F2 animals were observed. It is proposed that the maximum noneffective dose of ondansetron was 4 and 15 mg/kg with respect to general toxicity and reproductive capacity in F0 animals respectively. The maximum noneffective dose with respect to development in F1 and F2 animals was suggested to be 15 mg/kg./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The reproduction and developmental toxicity of ondansetron, a serotoninergic 5-HT3 receptor antagonist were studied in rats by oral administration of 1, 4, and 15 mg/kg of ondansetron daily during the gestation and lactation periods. The results suggest that the maximum noneffective dose of ondansetron for general and reproduction toxicity in dams was 15 mg/kg and that for developmental toxicity in fetuses and offspring was 4 mg/kg./LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ The reproduction and developmental toxicity of ondansetron, a serotoninergic 5-HT3 receptor antagonist, were studied in rats by IV administration of 0.5, 1.5, and 4 mg/kg of ondansetron daily during gestation and lactation period. The results suggest that the maximum noneffective dose of ondansetron for general toxicity in dams was 1.5 mg/kg and that for reproduction toxicity in dams and developmental toxicity in fetuses and offspring was 4 mg/kg.For more Non-Human Toxicity Excerpts (Complete) data for Ondansetron (10 total), please visit the HSDB record page. |
| Populations at Special Risk | Because clearance of ondansetron is decreased and apparent volume of distribution and plasma half-life are increased in patients with severe hepatic impairment, the drug should be used with caution and at reduced dosage in such patients.Because of the risk of QT-interval prolongation, ondansetron should be avoided in patients with congenital long QT syndrome. |
| Wassergefährdungsklasse (WGK) | 3 |
| UN-Transportnummer | UN 2811 6.1/PG 3 |
| Zollcode | 29339900 |
| RTECS-Nr. | FE6375500 |
| R-Sätze (R) | 25-36/37/38 |
| Toxizität | TDLo vn-man: 229 mg/kg/I LANCAO 344,190,94 |
| Gefahrensymbole | T,Xi |
| Sicherheitshinweise (S) | 45-37/39-26 |
| Lagerklasse | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Gefahrstoffdaten | 99614-02-5(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 3 OralAquatic Acute 1Aquatic Chronic 1Eye Dam. 1 |
Anwendungen & Verwendung
Beschreibung
Ondansetron (hydrochloride) (CRM) (Item No. 21710) is a certified reference material categorized as an antiemetic. Formulations containing ondansetron have been used to reduce alcohol consumption and mood disturbances in early-onset alcoholics. This product is intended for research and forensic applications.
Verwenden
antibacterial