Tetracycline

With a MIC value of 0.5 g/mL, tetracycline demonstrates susceptibility to V. vulnificus strain B3547[2].
Tetracycline breaks down pre-formed fibrils and prevents the formation of L-amyloid aggregates[3].

Mice with bacteremia are rescued from death by tetracycline (3 mg/kg; i.p. every 12 h until survive)[2].

Animal Model: 30 to 40 g female V. vulnificus strain B3547 infected ICR mice[2] Dosage: 3 mg/kg Administration: Intraperitoneal injection; 3 mg/kg every 12h until survive Result: prevented human CNE-2 xenografts from growing in nude mice.

Absorption, Distribution and Excretion
Bioavailability is less than 40% for intramuscular injection, 100% for intravenous injection, and 60-80% for oral administration (fasting adults). Food and/or milk can reduce the gastrointestinal absorption of oral tetracycline preparations by 50% or more. They are concentrated in the liver in bile and excreted in urine and feces in high concentrations of their biologically active form. All tetracyclines are adequately but incompletely absorbed by the gastrointestinal tract. Most absorption occurs in the stomach and upper small intestine, with the highest absorption rate on an empty stomach. /Tetracyclines/ … /Tetracycline/ Absorption is very incomplete. Peak plasma concentrations are reached within 2-4 hours after a single oral dose. A 250 mg dose every 6 hours results in a peak plasma concentration of approximately 2-2.5 μg/mL. The primary route of excretion for most tetracyclines is the kidneys, but they are also concentrated in the liver and excreted into the intestines via bile, where they are partially reabsorbed. Even when administered parenterally, the drug is cleared from the intestines via bile excretion. Tetracyclines
For more complete data on the absorption, distribution, and excretion of tetracyclines (16 in total), please visit the HSDB record page.

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Metabolism/Metabolites
Non-metabolizedBiological half-life
6–12 hours
/Its half-life/in the range of 6–12 hours…
Tetracycline was encapsulated in erythrocytes using dialysis. Encapsulation of 14C-labeled sucrose and 3H-labeled tetracycline reduced the encapsulation efficiency of tetracycline by drug concentration (0.2 mg/ml erythrocytes), but 14C-labeled sucrose had no effect. The tetracycline-containing carrier erythrocytes were re-injected into calves, and their pharmacokinetic constants were investigated. The drug has a half-life of 6.7 hours and an overall elimination constant of 0.104 hours. Serum half-life... is 6-12 hours in adults with normal renal function, and has been reported to be 57-120 hours in patients with severe renal impairment.

Interactions
Tetracycline itself has been shown to have a direct, pH-dependent effect on the rat intestine, leading to increased sulfamate absorption. Oral administration of ferrous sulfate (200-600 mg) interferes with gastrointestinal absorption of tetracycline and vice versa, resulting in decreased serum antibiotic and iron salt levels, respectively. Other iron salts, such as ferrous fumarate and ferrous gluconate, have been shown to interact with tetracycline. Two novel choleretic agents, α,α-diethyl-1-naphthacetic acid (DA 808) and α-methyl-α-(2-morpholinoethyl)-1-naphthacetic acid (DA 1627), increase tetracycline excretion in rat bile. Since DA 808 and DA 1627 do not decrease tetracycline concentrations in bile, they appear to act as true choleretics. ... Concomitant intake of dairy products, aluminum hydroxide gel, calcium, magnesium, iron, or zinc salts, and bismuth subsalicylate can impair the absorption of these drugs. The mechanism leading to reduced absorption appears to be the chelation of divalent and trivalent cations. /Tetracyclines/
For more complete data on interactions of tetracycline drugs (22 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats: 807 mg/kg
Oral LD50 in mice: 678 mg/kg
Oral LD50 in guinea pigs: 1875 mg/kg

[1]. Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology ofbacterial resistance. Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60.

[2]. Antibiotic efficacy against Vibrio vulnificus in the mouse: superiority of tetracycline. J Pharmacol Exp Ther. 1983 Jun;225(3):595-8.

[3]. Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 2001 Jan 5;487(3):404-7.

Tetracycline (oral) may cause developmental toxicity, depending on state or federal labeling requirements. Tetracycline is a broad-spectrum polyketide antibiotic produced by Streptomyces actinomycetes. It has multiple effects, including antibacterial, antiviral, antiantigenic, protein synthesis inhibitor, and E. coli metabolism inhibition. It is a tertiary α-hydroxy ketone, belonging to the tetracycline class of antibiotics. It is the conjugate acid of tetracycline (1-) and tetracycline zwitterion. Tetracycline is a broad-spectrum polyketide antibiotic produced by Streptomyces actinomycetes. It exerts its antibacterial effect by reversibly binding to the bacterial 30S ribosomal subunit, preventing aminoacyl-tRNA from binding to ribosome receptor sites. It can also bind to the bacterial 50S ribosomal subunit and may alter the cell membrane, leading to leakage of intracellular components from the bacterial cell. The U.S. Food and Drug Administration (FDA) has revoked marketing authorization for all tetracycline-containing oral liquid formulations for children at concentrations exceeding 25 mg/mL. Other formulations of tetracycline may continue to be used. Tetracycline is a tetracycline antibiotic. It is a broad-spectrum naphthocycloene antibiotic, semi-synthesized from chlortetracycline, an antibiotic isolated from Streptomyces aureofaciens. In bacteria, tetracycline binds to the 30S ribosomal subunit, interfering with the binding of aminoacyl-tRNA to the mRNA-ribosome complex, thereby inhibiting protein synthesis. A naphthocycloene antibiotic that inhibits the binding of aminoacyl-tRNA during protein synthesis. See also: tetracycline hydrochloride (in salt form); tetracycline phosphate complex (its active ingredient); tetracycline phosphate (its active ingredient)...see more...

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Drug Indications
Used to treat bacterial infections such as Rocky Mountain spotted fever, typhus, tick fever, Q fever, rickettsial pox, and Brill-Zinther's disease. It can be used to treat infections caused by Chlamydia spp. and Borrelia burgdorferi (Lyme disease), as well as upper respiratory tract infections caused by typical (Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis) and atypical pathogens (Chlamydia pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila). It can also be used to treat acne. Tetracycline may be an alternative for those allergic to penicillin.

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Mechanism of Action
Tetracycline passively diffuses through porin channels on bacterial membranes and reversibly binds to the 30S ribosomal subunit, preventing tRNA from binding to the mRNA-ribosome complex, thereby interfering with protein synthesis.
Tetracyclines are thought to inhibit protein synthesis by specifically binding to the 30S ribosome and preventing aminoacyl-tRNA from approaching the mRNA-ribosome complex. /Tetracycline/
...The reversible binding of the antibiotic may be the reason for its antibacterial action. Tetracyclines
Tetracyclines bind to cells and intracellular substances to form fluorophores that emit golden fluorescence under ultraviolet light. The fluorophore can remain in the bone for months.
Photosensitivity is thought to be caused by light energy acting on drugs and skin proteins, or altering their structure, thus forming antigens. These rashes require prior exposure to the sensitizing substance, are dose-independent, and cross-sensitivity exists with chemically related complications. /Tetracyclines/
For more complete data on the mechanisms of action of tetracyclines (6 in total), please visit the HSDB record page.

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Therapeutic Use
Antibiotics, Tetracyclines; Protein Synthesis Inhibitors
Tetracycline hydrochloride ointment is used for the prevention of minor bacterial skin infections and the treatment of skin ulcers. /Tetracycline Hydrochloride; Not included in the US product label/
Tetracycline hydrochloride ointment is indicated for the topical treatment of minor skin infections caused by streptococci, staphylococci, and other susceptible bacteria. /Tetracycline Hydrochloride; Included in the US product label/
Tetracycline hydrochloride topical solution is indicated for the topical treatment of acne vulgaris. It may be effective for grade II and III acne, which is characterized by inflammatory lesions such as papules and pustules. /Tetracycline hydrochloride; included in US product labeling/
For more complete data on the therapeutic uses of tetracyclines (37 in total), please visit the HSDB record page.

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Drug Warnings
Typical use of tetracyclines is not recommended except for ocular applications. /Tetracyclines/
Microorganisms resistant to one tetracycline are often also resistant to other tetracyclines. /Tetracyclines/
Cross-sensitization between different tetracyclines is common. Tetracyclines
…Nausea, vomiting, polyuria, polydipsia, proteinuria, acidosis, glycosuria, and severe aminoaciduria (a type of Fanconi syndrome) have been observed in patients taking expired or degraded tetracyclines.
For more complete data on warnings for tetracyclines (31 in total), please visit the HSDB record page.

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Pharmacodynamics
Tetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit, preventing aminoacyl-tRNA from binding to the A site of the ribosome. It can also bind to the 50S ribosomal subunit to some extent. This binding is inherently reversible. Furthermore, tetracycline may alter the bacterial cell membrane, leading to the leakage of intracellular substances such as nucleotides.

C22H4N2O8

444.4346

444.153

C, 59.46; H, 5.44; N, 6.30; O, 28.80

60-54-8

Tetracycline-d6;2373374-42-4;Tetracycline hydrochloride;64-75-5

54675776

Light yellow to yellow solid powder

1.3809

554.44°C

175-177 °C(lit.)

432.0±32.9 °C

0.0±2.9 mmHg at 25°C

1.6500

-1.47

6

9

2

32

971

5

O([H])[C@@]12C(=C(C(N([H])[H])=O)C([C@]([H])([C@]1([H])C([H])([H])[C@@]1([H])C(=C(C3C(=C([H])C([H])=C([H])C=3[C@@]1(C([H])([H])[H])O[H])O[H])O[H])C2=O)N(C([H])([H])[H])C([H])([H])[H])=O)O[H]

OFVLGDICTFRJMM-WESIUVDSSA-N

InChI=1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1

2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, (4S,4aS,5aS,6S,12aS)-

Mericycline; Micycline; Neocycline; NSC 108579; NSC-108579; NSC108579

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 89~125 mg/mL (200.25~281.26 mM)
Ethanol : ~22 mg/mL
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.68 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)