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Alosetron Hydrochloride
ALOSETRON HCL · Lotronex · GR 68755 · GR 68755X · GR 68755C · Alosetron hydrocloride · ALOSETRON HYDROCHLORIDE · Alosetron HCl - Bio-X ?
Identifikatoren & physikalische Daten
| CAS No. | 122852-69-1 |
|---|---|
| Summenformel | C17H19ClN4O |
| Durchschnittliche Molmasse | 330,8 g/mol |
| SMILES | Cc1[nH]cnc1CN1CCc2c(c3ccccc3n2C)C1=O.Cl |
| InChIKey | FNYQZOVOVDSGJH-UHFFFAOYSA-N |
| PubChem CID | 60758 |
| ChEMBL | CHEMBL1200885 |
| EC No. | 802-450-0 |
| DTXSID | DTXSID8044208 |
Chemische & physikalische Eigenschaften
| Polarare Oberfläche (TPSA) | 53,9 |
|---|---|
| H-Brücken-Donoren | 2 |
| H-Brücken-Akzeptoren | 2 |
| Frei drehbare Bindungen | 2 |
| Schwere Atome | 23 |
| Formalladung | 0 |
| Komplexität | 442 |
| Löslichkeit | White to beige solid with a solubility of 61 mg/ml in water, 42 mg/ml in 0.1M hydrochloric acid, 0.3 mg/ml in pH 6 phosphate buffer, and <0.1 mg/ml in pH 8 phosphate buffer /Hydrochloride/H2O: ≥5mg/mL at warmedH2O: ≥5mg/mL atwarmed |
| Human Drugs | FDA approved drugs -> Active ingredient |
| Schmelzpunkt | 288-291 °C288-291°C |
| Other Experimental Properties | Mol wt: 294.35. /Alosetron/ |
| Lagerbedingungen | 2-8°C |
| Aggregatzustand | powder |
| Farbe | white to beige |
| InChI | 1S/C17H18N4O.ClH/c1-11-13(19-10-18-11)9-21-8-7-15-16(17(21)22)12-5-3-4-6-14(12)20(15)2/h3-6,10H,7-9H2,1-2H3,(H,18,19)1H |
| InChIKey | FNYQZOVOVDSGJH-UHFFFAOYSA-N |
| SMILES | CN1C2=C(C=CC=C2)C3=C1CCN(CC4=C(C)N=CN4)C3=O.Cl |
| CAS Datenbank | 122852-69-1(CAS DataBase Reference) |
Sicherheit & Vorschriften
| GHS-Einstufung | DangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P264, P264+P265, P270, P273, P280, P301+P316, P305+P351+P338, P321, P330, P337+P317, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 43 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl alosetron hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Hazard Classes and Categories | Acute Tox. 3 (100%) |
| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| Wechselwirkungen | ... /A study was conducted/ to examine the potential for alosetron to alter the pharmacokinetics of theophylline by inhibiting its metab, as suggested by in vitro & in vivo effects on CYP1A2 activity. ... Ten healthy female volunteers received theophylline 200 mg twice daily alone for 8 days & with alosetron 1 mg twice daily for 15 days in this randomized, placebo-controlled, two-way-crossover study. ... Alosetron had no significant effect on theophylline plasma concns (Cmax approx 9 microg/ml), AUC approx 90 microg/ml-hr) or oral formation clearance of 3 major metabolites produced via CYP1A2: 3-methylxanthine, 1-methylurate & 1,3-dimethylurate (5, 7 & 16 ml/min, respectively). Concomitant admin of alosetron & theophylline was well tolerated. ... The absence of a clinical drug interaction involving inhibition of theophylline metab by alosetron was not predicted by in vitro & in vivo metabolic probe data. /Salt not specified/Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP2C9 & CYP3A4. Fluoxetine is an antidepressant that is administered as a racemic mixture of equipotent R- & S-enantiomers. Fluoxetine metab involves CYP2D6 & CYP2C9 in the formation of its major metabolite, norfluoxetine. This metabolite is also present as two enantiomers, of which only the S-enantiomer exhibits comparable antidepressant activity. This study was conducted to assess the potential for an effect of alosetron on the pharmacokinetics of fluoxetine. This was an open-label, two-period, nonrandomized, crossover study in 12 healthy female & male volunteers. The pharmacokinetics for both enantiomers of fluoxetine & norfluoxetine were examined following single oral doses of 20 mg fluoxetine, given alone & in combination with alosetron 1 mg twice daily for 15 days. The results showed small delays in peak concn but no clinically significant effect of alosetron on the pharmacokinetics of S- & R-fluoxetine or S- & R-norfluoxetine. Coadministration of alosetron & fluoxetine was well tolerated by all subjects.Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP 2C9 & 3A4. Alprazolam is a short-acting benzodiazepine commonly prescribed for the treatment of anxiety disorders & a potential comedication in patients with IBS. Alprazolam is extensively metabolized by CYP3A4. This clinical study was conducted to assess the potential for a metabolic drug interaction between these two CYP3A4 substrates. This was an open-label, randomized, two-period, crossover study in 12 healthy female & male volunteers to determine the effect of concomitant admin of alosetron at the recommended dose of 1 mg /orally/ bid on the pharmacokinetics of alprazolam following a single oral 1 mg dose. The results showed no effect of alosetron on the pharmacokinetics of alprazolam. Mean alprazolam AUC was 210 & 202 ng/h/ml in the absence & the presence of alosetron, respectively. Therefore, alprazolam may be safely coadministered with alosetron without the need for dosage adjustment. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)Alosetron hydrochloridevLess-DILI-concern4Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Wassergefährdungsklasse (WGK) | 3 |
| UN-Transportnummer | UN 2811 6.1 / PGIII |
| Zollcode | 2933790002 |
| R-Sätze (R) | 25-36-52/53 |
| Gefahrensymbole | T,Xi |
| Sicherheitshinweise (S) | 26-45 |
| Lagerklasse | 6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects |
| Gefahrstoffdaten | 122852-69-1(Hazardous Substances Data) |
| Gefahrenklasse | Acute Tox. 3 OralAquatic Chronic 3Eye Irrit. 2 |
Anwendungen & Verwendung
Beschreibung
Lotronex (alosetron) was developed for the treatment of severe irritable bowel syndrome (IBS), and was approved for use by the US Food and Drug Administration (FDA) in 2000. Although Lotronex had a relatively high improvement rate in patients taking the drug for IBS, it was voluntarily pulled from the market by GlaxoWellcome that same year due to reports of severe adverse side effects, some resulting in death. In 2002, Lotronex was reapproved in a supplemental New Drug Application for use under more restrictive conditions. Now with a risk management program to be consulted prior to administration of the drug, Lotronex is designated to be prescribed only when its medical benefits outweigh the risks of toxic effects; women with severe diarrhea-predominant IBS are now the focal point of prescriptions for Lotronex.
Verwenden
Alosetron hydrochloride is used in treatment of irritable bowel syndrome