Lincomycin

Pharmaceuticals -> Listed in ZINC15

Pharmaceuticals -> Antibiotics (Macrolides)

Pharmaceuticals -> Antibiotics

Pharmaceutical

freely soluble

Soluble in methanol, lower alcohols, acetone, ethyl acetate, chloroform. Slightly soluble in water

Soluble in methanol, ethanol, butanol, isopropanol, ethyl acetate, n-butyl acetate, amyl acetate, etc. Moderately soluble in water.

Active Ingredients (Lincomycin) -> FDA Greenbook

Pharmaceuticals -> UK Veterinary Medicines Directorate List

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

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/

Positive

3.72

2.91

Sciex API4000

Electrospray ionization

formic acid (10nM)

This chemical does not meet GHS hazard criteria for 91.7% (11 of 12) of all reports.

Not Classified

Aggregated GHS information provided per 12 reports by companies from 2 notifications to the ECHA C&L Inventory.

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.

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.

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 °C; freezing should be avoided.

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.

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.

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.

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.

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.

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.

EC50; Species: Pseudokirchneriella subcapitata (Green Algae) exponential growth phase 1000 cells/mL; Conditions: freshwater, static, 25 °C, dissolved oxygen >90% saturated; Concentration: 70 ug/L for 3 days (95% confidence interval: 50-100 ug/L); Effect: decreased population abundance />99% purity formulation/

EC50; Species: Ceriodaphnia dubia (Water Flea) age <24 hr; Conditions: freshwater, renewal, 25 °C, dissolved oxygen >90% saturated; Concentration: 7200 ug/L for 48 hr (95% confidence interval: 4800-11660 ug/L); Effect: decreased population abundance />99% purity formulation/

EC50; Species: Ceriodaphnia dubia (Water Flea) age <24 hr; Conditions: freshwater, static, 25 °C; Concentration: 13980 ug/L for 24 hr (95% confidence interval: 11360-17200 ug/L); Effect: intoxication, immobilization />99% purity formulation/

EC50; Species: Daphnia magna (Water Flea) neonate age <24 hr; Conditions: freshwater, static, 20 °C; Concentration: 23180 ug/L for 24 hr (95% confidence interval: 18960-28330 ug/L); Effect: intoxication, immobilization />99% purity formulation/

EC50; Species: Lemna gibba (Inflated Duckweed); Conditions: freshwater, renewal, 25 °C; Concentration: >1000 ug/L for 7 days; Effect: decreased population biomass /formulation/

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.

/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.

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)

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).

/SIGNS AND SYMPTOMS/ Admin of lincomycin, particularly orally, can cause diarrhea in as many as 20% of cases; diarrhea 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.

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.

J01FF02

J - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Lincomycin serum protein binding varies greatly depending on the dose, ranging from 28 to 86% in one study, and generally decreases with increasing serum concentration suggesting saturable binding. It has been suggested that lincomycin, like [clindamycin], is primarily bound to α1-acid glycoprotein, which is consistent with later studies in humans and animals.

Lincomycin is a lincosamide antibiotic derived as a natural fermentation product from _Streptomyces lincolnensis_. Like [clindamycin], lincomycin is active against Gram-positive cocci and bacilli as well as Gram-negative cocci and some other organisms such as _Haemophilus_ spp. It is also effective against anaerobic bacteria, though in this regard [clindamycin] is generally more potent. Prescribing information highlights that the range of clinically confirmed effectiveness is largely limited to _Staphylococcus_ spp. and _Streptococcus_ spp., with additional activity noted _in vitro_. Lincomycin should be used with caution due to its association with severe cutaneous hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and acute generalized exanthematous pustulosis, and its potential to precipitate _Clostridium difficile_ associated diarrhea (CDAD), which may lead to fatal colitis. Special care should therefore be exercised when used in elderly patients, individuals with a history of gastrointestinal disease, and those with a history of asthma or significant allergies. Lincomycin for injection may contain benzyl alcohol as a preservative, which has been associated with gasping syndrome in pediatric patients. The serum half-life is extended in patients with hepatic/renal impairment and may require dose adjustments and additional monitoring. Like all antibiotics, lincomycin use may cause overgrowth of non-susceptible organisms, which should be considered.

Lincomycin contains the unusual amino acid moiety propyl hygric acid linked to the sugar moiety α-methylthiolincosamine (α-MTL) that, like other lincosamides, functions as a structural analogue of the 3' end of L-Pro-Met-tRNA and deacylated-tRNA to interact with the 23S rRNA of the 50S bacterial ribosomal subunit. Detailed investigations into the mechanism of the related lincosamide [clindamycin] suggested a two-phase binding, instantaneously to the A-site with a shift in equilibrium towards the P-site over several seconds. This shift appears to be due to rotation of the propyl hygric acid moiety, while the α-MTL remains relatively stationary. Recent crystal structures of lincomycin in complex with the 50S ribosomal subunit of _Staphylococcus aureus_ show that the α-MTL moiety forms hydrogen bonds with C2611, A2058, G2505, A2059, and G2503 of the 23S rRNA while the propyl hygric acid moiety interacts only through van der Waals contacts, suggesting it may be free to rotate similar to [clindamycin]. This mechanism is supported by the observation that the most common resistance mechanism, which also affects macrolides and streptogramin B (MSLB resistance) involves methylation of A2058; other resistance mechanisms similarly target residues such as A2058, A2059, and C2611.

Lincomycin may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of infection and the susceptibility of the infecting organism. Lincomycin appears to inhibit protein synthesis in susceptible organisms by binding to 50S ribosomal subunits; the primary effect is inhibition of peptide bond formation. The site of action appears to be the same as that of clindamycin, erythromycin, and chloramphenicol.

/The authors/ ... investigated the inhibition of peptide bond formation by the antibiotic lincomycin, at 150 mM NH4Cl. /The authors/ ... used an in vitro system in which a ribosomal ternary complex, the acetyl[3H] phenylalanine-tRNA-70 S ribosome-poly(U) complex (complex C), reacts with puromycin, forming peptide bonds. Complex C can be considered an analog of the elongating ribosomal complex and puromycin an analog of aminoacyl-tRNA. In a previous study /the authors/ ... reported on the kinetics of inhibition by lincomycin at 100 mM NH4Cl. In the present investigation, /the authors/ ... find that an increase of the ammonium ion concentration to 150 mM causes profound changes in the kinetic behavior of the system, which can be summarized as follows. First, the association rate for complex C and lincomycin is increased. At a lincomycin concentration of 10 uM the apparent equilibration rate constant is 4.3 min-1 at 100 mM NH4Cl, whereas it becomes 6.7 min-1 at 150 mM. Second, at 150 mM NH4Cl, with increasing concentrations of lincomycin, there is a transition from competitive to mixed-noncompetitive inhibition. The prevailing notion is that lincomycin acts at the ribosomal A-site, a mechanism that agrees only with competitive kinetics (mutually exclusive binding between puromycin and lincomycin). At the molecular level, the change in the kinetics of inhibition that we observe may mean that the mutually exclusive binding between aminoacyl-tRNA and lincomycin is converted to simultaneous binding, as a result of conformational changes occurring in the elongating ribosomal complex.

Lincomycin has a biological half-life of 5.4 ± 1.0 hours following intramuscular or intravenous administration, which is prolonged in patients with impaired hepatic or renal function.

The plasma half-life of lincomycin is 4-6.4 hours in patients with normal renal function. The plasma half-life is increased in proportion to the degree of impairment in patients with reduced renal or hepatic function.100 Plasma half-lives as high as 3 times normal have been reported in patients with severe renal impairment. The half-life may be 2 times normal in patients with hepatic impairment.

Lincomycin metabolism is poorly defined, though the primary product recovered following administration in humans is unchanged lincomycin.

Lincomycin is partially metabolized in the liver and both drug and metabolites are excreted in urine, bile, and feces.

Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.

Substances that inhibit the growth or reproduction of BACTERIA.

A 600 mg dose of lincomycin administered over two hours intravenously results in an average Cmax of 15.9 μg/mL while the same dose given by intramuscular injection produces an average Cmax of 11.6 μg/mL after 60 minutes. Lincomycin administered intramuscularly to healthy adult male volunteers in doses between 600 and 1500 mg had an AUC0-∞ between 92.22 and 159.91 μg\*h/mL. A similar study using intravenous infusion of 600-2400 mg lincomycin found AUC0-∞ values between 72.5 and 212.8 μg\*h/mL. Overall, the AUC increases disproportionally to dose.

Following a 600 mg dose of lincomycin given either intramuscularly or intravenously, the urinary excretion ranges from 1.8-30.3% of the administered dose. Bile is also thought to be an important route of elimination. Dose adjustments are required in patients with either renal or hepatic impairment.

Lincomycin administered intravenously to healthy adult males had a steady-state volume of distribution of 63.8 ± 23.8, 78.8 ± 17.0, and 105.1 ± 43.1 L for 600, 1200, and 2400 mg doses, respectively.

Lincomycin administered intravenously to healthy adult males had a clearance of 9.9 ± 2.5, 10.0 ± 2.0, and 11.8 ± 2.4 L/h for 600, 1200, and 2400 mg doses, respectively.

Lincomycin is rapidly but only partially (20 to 35%) absorbed from gi tract ... Peak plasma concn avg 2 to 5 ug/mL after oral dose of 500 mg; values maintained ... for most gram-pos microorganisms for 6 to 8 hr, and detectable antibacterial activity persists for 12 hr or more. Im injection results in max plasma concn within 30 min.

Urinary excretion ... is limited and quite variable; about 5% of oral dose and 15% of parenteral dose appear in urine. The bile is important route of excretion of ... antibiotic. Drug appears in active form in feces after oral and parenteral admin, suggesting excretion in bile, through intestinal wall or both.

MEDICATION

MEDICATION (VET)

Lincomycin was produced originally by the actinomycete Streptomyces lincolnensis var. lincolnensis, NRRL 2936. Subsequently, it has been produced by a variety of Streptomyces strains and by strain 1146 of Actinomyces roseolus. Extraction by standard procedures using Sarcina lutea as the assay organism on agar trays leads to a crystalline hydrochloride having molecular formula C18-H34-N2-O6-S.HCl.1/2 H2O. A second, more dense form exists as the monohydrate, and this latter form of lincomycin hydrochloride is the Upjohn trademarked Lincocin available commercially.

... Produced by streptomyces lincolnensis var lincolnensis.

Antibiotics are fermentation products and are isolated either as unfinished products or as intermediates, generally solid substances of limited stability. They are purified by methods normally employed in organic chemistry, which include chromatography, crystallization, and precipitation. /Antibiotics/

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Veterinary Drug -> ANTIMICROBIAL_AGENT -> JECFA Functional Classes

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan