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Lincomycin
Lincomycine · Lincomycin hydrochoride · methyl6,8-dideoxy-6-(1-methyl-4-propyl-2-pyrrolidinecarboxamido)-1-thio-d-eryt · D-erythro-alpha-D-galacto-Octopyranoside, methyl 6,8-dideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]-1-thio-, (2S-trans)- · (2S,4R)-N-((1R,2R)-2-Hydroxy-1-((2R,3R,4S,5R,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)propyl)-1-methyl-4-propylpyrrolidine-2-carboxamide · U-10149 · Myvicin · U-10149A
Identifikatoren & physikalische Daten
| CAS No. | 154-21-2 |
|---|---|
| Summenformel | C18H34N2O6S |
| Durchschnittliche Molmasse | 406,5 g/mol |
| Monoisotopische Masse | 406,21375781 g/mol |
| SMILES | CCC[C@@H]1C[C@@H](C(=O)N[C@@H]([C@H]2O[C@H](SC)[C@H](O)[C@@H](O)[C@H]2O)[C@@H](C)O)N(C)C1 |
| InChIKey | OJMMVQQUTAEWLP-KIDUDLJLSA-N |
| PubChem CID | 3000540 |
| ChEMBL | CHEMBL1447 |
| ChEBI | CHEBI:6472 |
| EC No. | 205-824-6 |
| DTXSID | DTXSID3023215 |
| Lokaler Name | Lincomycin |
Chemische & physikalische Eigenschaften
| XLogP | 0,2 |
|---|---|
| Polarare Oberfläche (TPSA) | 148 |
| H-Brücken-Donoren | 5 |
| H-Brücken-Akzeptoren | 8 |
| Frei drehbare Bindungen | 7 |
| Schwere Atome | 27 |
| Formalladung | 0 |
| Komplexität | 498 |
| Stoffklassen | Other Uses -> Pharmaceuticals |
| Arzneimittel | Pharmaceuticals -> Listed in ZINC15Pharmaceuticals -> Antibiotics (Macrolides)Pharmaceuticals -> Antibiotics |
| LogP (Verteilungskoeffizient) | log Kow = 0.20 |
| Color/Form | Amorphous solid |
| Löslichkeit | freely solubleSoluble in methanol, lower alcohols, acetone, ethyl acetate, chloroform. Slightly soluble in waterSoluble in methanol, ethanol, butanol, isopropanol, ethyl acetate, n-butyl acetate, amyl acetate, etc. Moderately soluble in water.Aqueous Acid (Slightly), DMSO (Slightly), Methanol (Slightly), Water |
| Animal Drugs | Active Ingredients (Lincomycin) -> FDA GreenbookPharmaceuticals -> UK Veterinary Medicines Directorate ListPharmaceuticals -> Animal Drugs -> Approved in Taiwan |
| Decomposition | When heated to decomposition it emits very toxic fumes of /oxides of sulfur and oxides of nitrogen/. |
| Schmelzpunkt | 187-190148-150°C |
| Optical Rotation | White or almost white crystalline powder, odorless or with a slight mercaptan-like odor and bitter taste, mp 156-158 °C. Specific optical rotation = +143 deg at 25 °C/D (water). pH of 1% aqueous solution = 4.8 /Lincomycin hydrochloride monohydrate/ |
| Stability/Shelf Life | Stable in light and air. /Lincomycin HCl, USP/ |
| Ionization Efficiency | Positive3.722.91Sciex API4000Electrospray ionizationformic acid (10nM) |
| Dissociation Constants | pKa = 7.6 |
| Siedepunkt | 646.8±55.0 °C(Predicted) |
| Dichte | 1.1704 (rough estimate) |
| Brechungsindex | 1.6510 (estimate) |
| Lagerbedingungen | Hygroscopic, -20°C Freezer, Under inert atmosphere |
| pKa (Säurekonstante) | 7.6(at 25℃) |
| Aggregatzustand | Solid |
| Farbe | White to Off-White |
| Henry-Konstante | 3.3×1017 mol/(m3Pa) at 25℃, HSDB (2015) |
| Stabilität | Hygroscopic |
| InChIKey | POUMFISTNHIPTI-KADGABRTNA-N |
| SMILES | [C@H]1([C@H](O)[C@@H]([C@@H](O)[C@@H](SC)O1)O)[C@@H]([C@H](O)C)NC(=O)[C@H]1N(C)C[C@H](CCC)C1.Cl |&1:0,1,3,4,6,11,12,18,22,r| |
| NIST chemische Informationen | Lincomycin(154-21-2) |
| EPA chemische Informationen | Lincomycin (154-21-2) |
Sicherheit & Vorschriften
| GHS-Einstufung | This chemical does not meet GHS hazard criteria for 91.7% (11 of 12) of all reports.Not ClassifiedAggregated GHS information provided per 12 reports by companies from 2 notifications to the ECHA C&L Inventory. |
|---|---|
| Weitere Sicherheitsinformationen | IMAP assessments - D-erythro-.alpha.-D-galacto-Octopyranoside, methyl 6,8-dideoxy-6-[[(1-methyl-4-propyl-2-pyrrolidinyl)carbonyl]amino]-1-thio-, (2S-trans)-: Environment tier I assessment |
| Gefahrenübersicht | Allergic contact dermatitis reported in poultry and pig breeders[Kanerva, p. 1158] |
| FDA-Anforderungen | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl lincomycin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Lincomycin hydrochloride/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Lincomycin is included on this list.The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Lincomycin hydrochloride is included on this list. /Lincomycin hydrochloride/The Generic Animal Drug and Patent Restoration act requires that each sponsor of an approved animal drug must submit to the FDA certain information regarding patents held for the animal drug or its method of use. The Act requires that this information, as well as a list of all animal drug products approved for safety and effectiveness, be made available to the public. Lincomycin hydrochloride monohydrate is included on this list. /Lincomycin hydrochloride monohydrate/For more FDA Requirements (Complete) data for LINCOMYCIN (9 total), please visit the HSDB record page. |
| Hazard Classes and Categories | Not Classified |
| Brandbekämpfungsverfahren | As with all fires, evacuate personnel to a safe area. Firefighters should use self-contained breathing equipment and protective clothing.Water spray, dry chemical, carbon dioxide, or foam as appropriate for surrounding fire and materials. |
| Lagerbedingungen | Store in tight, light-resistant container as defined in the USP-NF. This material should be handled and stored per label instructions to ensure product integrity. Store in a cold place.Lincomycin hydrochloride injection should be stored at 20-25 °Cfreezing should be avoided. |
| Reinigungsverfahren | Wear approved respiratory protection, chemically compatible gloves, and protective clothing. Wipe up spillage or collect spillage using a high-efficiency vacuum cleaner. Avoid breathing dust. Place spillage in appropriately labeled container for disposal. Wash spill site. |
| Entsorgungsverfahren | SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.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. |
| Preventive Measures | As a general rule, when handling USP Reference Standards, avoid all contact and inhalation of dust, mists, and/or vapors associated with the material. Wash thoroughly after handling.As with all dry powders, it is advisable to ground mechanical equipment in contact with dry material to dissipate the potential buildup of static electricity.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. |
| Allowable Tolerances | Tolerances for residues of new animal drugs in food. Lincomycin. (a) Acceptable daily intake (ADI). The ADI for total residues of lincomycin is 25 micrograms per kilogram of body weight per day. (b)Chickens. A tolerance for residues of lincomycin in chickens is not required. (c) Swine. Tolerances for lincomycin of 0.6 part per million in liver and 0.1 part per million in muscle are established. |
| Personal Protective Equipment (PPE) | Respiratory protection: Use a NIOSH-approved respirator, if it is determined to be necessary by an industrial hygiene survey involving air monitoring. In the event that a respirator is not required, an approved dust mask should be used. Gloves: Chemically compatible. Eye protection: Safety glasses or goggles. Protective clothing: Protect exposed skin.Engineering controls such as exhaust ventilation are recommended. |
| Körperbelastung | Lincomycin is distributed into milkconcentrations of 0.5-2.4 ug/mL have been reported in human milk. |
| Wechselwirkungen | Lincomycin has been shown to have neuromuscular blocking properties that may enhance the neuromuscular blocking action of other agents (e.g., ether, tubocurarine, pancuronium). Lincomycin should be used with caution in patients receiving such agents.When administered concomitantly, kaolin reduces the GI absorption of lincomycin by as much as 90%, resulting in decreased plasma concentrations of the antibiotic. If administration of both drugs is necessary, patients should receive kaolin at least 2 hours before lincomycin.Because of reported in vitro antagonism between lincomycin and erythromycin, the drugs should not be used concomitantly.Antiperistaltic agents, such as opiates, difenoxin, diphenoxylate, or loperamide, may prolong or worsen pseudomembranous colitis by delaying toxin elimination. |
| Ökotoxizitätswerte | EC50Species: Pseudokirchneriella subcapitata (Green Algae) exponential growth phase 1000 cells/mLConditions: freshwater, static, 25 °C, dissolved oxygen >90% saturatedConcentration: 70 ug/L for 3 days (95% confidence interval: 50-100 ug/L)Effect: decreased population abundance />99% purity formulation/Species: Ceriodaphnia dubia (Water Flea) age <24 hrConditions: freshwater, renewal, 25 °C, dissolved oxygen >90% saturatedConcentration: 7200 ug/L for 48 hr (95% confidence interval: 4800-11660 ug/L)Conditions: freshwater, static, 25 °CConcentration: 13980 ug/L for 24 hr (95% confidence interval: 11360-17200 ug/L)Effect: intoxication, immobilization />99% purity formulation/Species: Daphnia magna (Water Flea) neonate age <24 hrConditions: freshwater, static, 20 °CConcentration: 23180 ug/L for 24 hr (95% confidence interval: 18960-28330 ug/L)Species: Lemna gibba (Inflated Duckweed)Conditions: freshwater, renewal, 25 °CConcentration: >1000 ug/L for 7 daysEffect: decreased population biomass /formulation/ |
| Umweltverhalten | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 31(SRC), determined from a log Kow of 0.20(2) and a regression-derived equation(3), indicates that lincomycin is expected to have high mobility in soil(SRC). However, the pKa of lincomycin is 7.6(4), indicating that this compound will partially exist in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). Volatilization of lincomycin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 3.0X10-23 atm-cu m/mole(SRC), using a fragment constant estimation method(6). Lincomycin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.3X10-17 mm Hg(SRC), determined from a fragment constant method(7). The class of aminoglycosides, of which lincomycin is a member, were found to have biodegradation half-lives of about 30 days(8).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 69(SRC), determined from a log Kow of 0.20(2) and a regression-derived equation(3), indicates that lincomycin is not expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(4) based upon an estimated Henry's Law constant of 3.0X10-23 atm-cu m/mole(SRC), developed using a fragment constant estimation method(5). According to a classification scheme(6), an estimated BCF of 3(SRC), from its log Kow(2) and a regression-derived equation(3), suggests the potential for bioconcentration in aquatic organisms is low(SRC). The class of aminoglycosides, of which lincomycin is a member, were found to have biodegradation half-lives of about 30 days(7).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), lincomycin, which has an estimated vapor pressure of 1.3X10-17 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. |
| Unerwünschte Wirkungen | Skin Sensitizer - An agent that can induce an allergic reaction in the skin. |
| Milk Concentrations | Lincomycin is distributed into milkconcentrations of 0.5-2.4 ug/mL have been reported in human milk. |
| Ökotoxizitätsauszüge | /AQUATIC SPECIES/ ...The effects of eight common veterinary antibiotics /(including lincomycin)/ on anaerobic activity were studied. Anaerobic microcosms, prepared from freshly collected lagoon slurries, were amended with individual antibiotics at 10 mg/L for the initial screening study and at 1, 5, and 25 mg/L for the dose-response study. Monitored metabolic indicators included hydrogen, methane, and volatile fatty acid concentrations as well as chemical oxygen demand. The selected antibiotics significantly inhibited methane production relative to unamended controls, thus indicating that antibiotics at concentrations commonly found in swine lagoons can negatively impact anaerobic metabolism. Additionally, historical antibiotic usage seems to be a potential factor in affecting methane production. Specifically, less inhibition of methane production was noted in samples taken from the lagoon with a history of multiple-antibiotic use. |
| Effluent Concentrations | Flush water from a swine confined-feeding operation could contain as much as 116 ug/L of lincomycin based on feeding rates and a 30 minute flush/day from 2500 pigs with average weight of 180 lbs(1). Lincomycin was detected at <0.01 ug/L in effluent from a waste water facility near Phoenix, AZ taken on May 29, 2001(2). Analysis of seven wastewater treatment plants in Wisconsin revealed an average effluent concentration of 0.51 ug/L. The average influent concentration was 0.36 ug/L (quantitation limit = 0.05 ug/L)(3). Lincomycin was one of the main pollutants detected at concentrations >10 ug/L in influent of 5 wastewater treatment plants located in the large industrial city of Ulsan, Korea(5).Lincomycin concentrations in 12 municipal, four livestock, four hospital, and four pharmaceutical manufacture wastewater treatment plants(1) |
| Soil Adsorption/Mobility | The Koc of lincomycin is estimated as 69(SRC), using a log Kow of 0.20(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that lincomycin is expected to have high mobility in soil. However, the pKa of lincomycin is 7.80(4), indicating that this compound will exist partially in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5). |
| Natural Pollution Sources | Lincomycin is produced by the soil microorganism Streptomyces lincolnensis(1). |
| Human Toxicity Excerpts | /SIGNS AND SYMPTOMS/ Admin of lincomycin, particularly orally, can cause diarrhea in as many as 20% of casesdiarrhea may be severe, requiring withdrawal of drug, and some patients develop pseudomembranous colitis, which may be fatal./SIGNS AND SYMPTOMS/ ... Other rare untoward effects ... /include/ angioedema, serum sickness, anaphylaxis, photosensitivity, and cardiopulmonary arrest (after rapid intravenous infusion)./SIGNS AND SYMPTOMS/ Patients should be advised that antibacterials (including lincomycin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold). Patients also should be advised about the importance of completing the full course of therapy, even if feeling better after a few days, and that skipping doses or not completing therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with lincomycin or other antibacterials in the future./SIGNS AND SYMPTOMS/ Rapid IV administration of lincomycin has caused hypotension, syncope, and rarely cardiopulmonary arrest. Severe cardiopulmonary reactions have occurred when lincomycin was administered in higher concentrations at rates of administration that were higher than recommended.For more Human Toxicity Excerpts (Complete) data for LINCOMYCIN (12 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Lincomycin's production and use as an antibiotic(1) may result in its release to the environment through various waste streams(SRC). |
| Toxizität | LD50 oral in rat: 1gm/kg |
| Gefahrstoffdaten | 154-21-2(Hazardous Substances Data) |
Anwendungen & Verwendung
Beschreibung
Lincomycin is an antibiotic active against grampositive bacteria. Occupational exposure occurs in poultry and pig breeders.
Verwenden
Lincomycin is a polar, water soluble, broad spectrum antibiotic first isolated from Streptomyces licolnensis by researchers at Upjohn in 1962. Lincomycin was the first of a unique structural class, the lincosamides, containing a rare amino acid, 4-propyl-N-methylproline, coupled to an equally rare aminomethylthio-octopyranoside sugar. Lincomycin and semi-synthetic analogues are often incorrectly considered to be aminoglycosides but share little or no structural similarity. Lincomycin is a broad spectrum antibiotic with activity against anaerobic bacteria and protozoans. Lincomycin acts by binding to the 23S ribosomal subunit, blocking protein synthesis. Lincomycin has been extensively studied with over 7,000 literature citations.