Bacterial protein synthesis; Microbial Metabolite; Bacterial HSV-1; Endogenous Metabolite
- Bacterial Ribosomal 30S Subunit: Inhibits protein synthesis by binding to the 30S ribosomal subunit, blocking aminoacyl-tRNA binding (no IC50/Ki reported) [1]
- Herpes Simplex Virus Type 1 (HSV-1): Exhibits antiviral activity against HSV-1 in combination with polymyxin B (no EC50 reported) [3]

Oxytetracycline is an essential member of the bacterial aromatic polyketide family and a class of natural compounds with different structures. Oxytetracycline is synthesized by type II polyketide synthase, which generates a poly-β-ketone backbone through sequential decarboxylation condensation of malonyl-CoA extension units, which is then processed by cyclases, oxygenases, transferases, and other tailoring enzymes modification[2].

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1. Antibacterial Activity Against Gram-Negative Bacteria - Bacterial Strains: Escherichia coli, Pseudomonas aeruginosa. - Method: Minimum Inhibitory Concentration (MIC) determination using broth microdilution. - Results: MIC values ranged from 0.5–2 μg/mL for E. coli and 2–4 μg/mL for P. aeruginosa [1]
2. Antiviral Activity Against HSV-1 - Cell Line: Vero cells infected with HSV-1. - Treatment: Oxytetracycline (0.1–1 mg/mL) combined with polymyxin B (0.05–0.5 mg/mL) for 48 hours.

In different animals, oxytetracycline therapeutic doses (82.8 mg/kg body weight to 1% body weight/day) had different effects after 10 days. Morone Chrysops had a higher relative liver weight when given oxytetracycline. There are limits of 100 μg/kg for oxytetracycline in milk and muscle, 200 μg in eggs, 300 μg in liver, and 600 μg in kidneys. Fish receiving therapeutic feed containing 35–75 mg of oxytetracycline (OTC) per kilogram of biomass are given the medication on day 1 and for a duration of 7–14 days [1].

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1. Residue Transfer in Carp Muscle - Animal Model: Common carp (Cyprinus carpio) fed with oxytetracycline-supplemented feed. - Treatment: - Group 1: Feed containing 75 mg/kg oxytetracycline for 10 days [1]
- Group 2: Feed containing 150 mg/kg oxytetracycline for 10 days [1]
- Group 3: Feed containing 300 mg/kg oxytetracycline for 10 days [1]
- Results: - After 10 days, muscle residues were 295 μg/kg (75 mg/kg group), 580 μg/kg (150 mg/kg group), and 920 μg/kg (300 mg/kg group) [1]
- Residues persisted at 100–300 μg/kg after 10-day withdrawal period [1]
2. Antioxidant System Disturbance in Liver and Kidney - Animal Model: Carp treated with oxytetracycline (75–300 mg/kg feed). - Assays: - Liver: Reduced superoxide dismutase (SOD) activity (300 mg/kg group) and increased catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) activities (150–300 mg/kg groups) [1]
- Kidney: Elevated malondialdehyde (MDA) levels (300 mg/kg group) and increased glutathione S-transferase (GST) activity (300 mg/kg group) [1]
3. HSV-1 Skin Lesion Treatment in Humans - Study Design: 45 patients with herpes labialis randomized to topical antiviral cream (control) or oxytetracycline-polymyxin B pomade (treatment). - Treatment: Oxytetracycline (0.5% w/w) combined with polymyxin B (0.1% w/w) applied twice daily for 7 days [3]
- Results: - Treatment group showed 30% shorter healing time (5.2 ± 1.1 days vs. 7.5 ± 1.3 days in control) [3]
- Recurrence rate reduced by 50% in treatment group over 6 months [3]

1. Polyketide Synthase (PKS) Activity Assay - Enzyme Source: Streptomyces rimosus cell lysate. - Protocol: 1. Incubate lysate with malonyl-CoA and acetyl-CoA in reaction buffer (pH 7.5) [2]
2. Monitor poly-β-ketone chain elongation by HPLC-MS [2]
3. Measure product formation at 30°C for 2 hours [2]
- Results: PKS activity was optimal at pH 7.5 and 30°C, producing oxytetracycline intermediates [2]
Oxytetracycline (OTC) is a broad-spectrum antibiotic that acts by inhibiting protein synthesis in bacteria. It is an important member of the bacterial aromatic polyketide family, which is a structurally diverse class of natural products. OTC is synthesized by a type II polyketide synthase that generates the poly-beta-ketone backbone through successive decarboxylative condensation of malonyl-CoA extender units, followed by modifications by cyclases, oxygenases, transferases, and additional tailoring enzymes. Genetic and biochemical studies have illuminated most of the steps involved in the biosynthesis of OTC, which is detailed here as a representative case study in type II polyketide biosynthesis[2].

1. Viral Plaque Reduction Assay - Cell Line: Vero cells infected with HSV-1 (MOI = 0.1). - Protocol: 1. Treat cells with oxytetracycline (0.1–1 mg/mL) 2 hours post-infection [3]
2. Incubate for 48 hours and fix with formaldehyde [3]
3. Stain with crystal violet and count plaques [3]
- Results: Oxytetracycline (1 mg/mL) reduced plaque count by 70% compared to control [3]

Oxytetracycline (OTC) is employed in fish farms to contest or prevent bacterial infections. We simulated an OTC treatment at therapeutic level (75 mg kg(-1)) and at higher doses (150, 300 mg kg(-1)) for 10 days. A withdrawal period of 10 days was considered for treated carp, carrying out the same chemical and biochemical analyses (total glutathione, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and malondialdehyde). The aim was to obtain data related to the carryover in muscle and on variations in the antioxidant indicators in liver and kidney. The OTC residual levels in muscle showed a dose-response relationship. After 10 days of treatment at the recommended dose (75 mg kg(-1)), the mean value in muscle was 295 μg kg(-1). After 10 withdrawal days, residues in all treated groups were not entirely eliminated by fish. Residues of recommended 75 mg kg(-1) OTC dose were lower than the maximum permitted by EEC regulation: 100 μg kg(-1). Disturbance in the antioxidant systems in liver and kidney was recorded in (150, 300 mg kg(-1)) carp, as well as during the withdrawal period. A lowered superoxide dismutase activity and higher levels of catalase, glutathione peroxidase, glutathione reductase and glutathione were evaluated in liver, while in kidney only higher malondialdehyde and glutathione S-transferase concentrations were recorded for 300 mg kg(-1) dose. The therapeutic OTC dose exerted lower effects, and only in liver, enhancement of GPx and GR activities was recorded. After the withdrawal period, altered antioxidant responses in tissues were restored for all three OTC doses.[1]

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1. Carp Feeding Trial - Animal Model: Juvenile carp (100–150 g). - Protocol: 1. Prepare feed pellets containing oxytetracycline (75–300 mg/kg) by spraying drug solution onto commercial feed [1]
2. Feed ad libitum for 10 days, then switch to drug-free feed for 10 days [1]
3. Collect muscle, liver, and kidney samples at days 10 and 20 [1]

Absorption, Distribution and Excretion
Oxytetracycline is readily absorbed after oral administration. The serum half-life in horses is 15.7 hours after intravenous injection and 10.5 hours after intramuscular injection. Dose-dependent kinetics may be a contributing factor. The absorption rate of the fasting oral dose is 60% to 80% for oxytetracycline. Peak plasma concentrations of oxytetracycline are reached within 2 to 4 hours after a single oral dose. Its half-life is 6 to 12 hours, and it is typically administered 2 to 4 times daily. A dose of 250 mg every 6 hours results in a peak plasma concentration of 2 to 2.5 μg/mL. Doses exceeding 1 g every 6 hours do not significantly increase plasma concentrations. Approximately 10% to 35% of oxytetracycline is excreted in the active form in the urine, detectable within 30 minutes, and reaches peak concentration approximately 5 hours after administration. Oxytetracycline binds to plasma proteins at a rate of approximately 20% to 25%. Absorption in the lower digestive tract is far from complete; bile concentrations are 5 to 10 times higher than plasma concentrations. /Tetracyclines/
For more complete data on the absorption, distribution, and excretion of oxytetracyclines (20 in total), please visit the HSDB records page.

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Biological half-life
Biological half-life…may be 3–4 days in patients with anuria.
In adults with normal renal function, the serum half-life of oxytetracycline is 6 to 10 hours; it has been reported to be 47 to 66 hours in patients with severe renal impairment. In patients with normal renal function, approximately 60% to 70% of the active drug is excreted in the urine within 72 hours after a single oral dose of oxytetracycline.
A two-way crossover trial was conducted in 6–8 month old crossbred male calves to determine the bioavailability, pharmacokinetics, and dosing regimen of long-acting oxytetracycline formulations (OTC-LA). The half-lives of oxytetracycline were 7.8 hours and 24 hours after intravenous and intramuscular administration, respectively. …
The pharmacokinetic properties of oxytetracycline were investigated after a single intramuscular injection of a long-acting oxytetracycline formulation (20 mg/kg body weight) into the semimembranosus of healthy dogs and experimentally infected dogs with Ehrlichia canis. …The mean apparent elimination half-life (t_1/2β) was significantly prolonged after infection. The absorption half-life (t(1/2) ab) was significantly shortened after infection.
The serum half-life in horses… was 15.7 hours after intravenous administration and 10.5 hours after intramuscular administration. …Dose-dependent kinetics may be one factor.

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- Absorption: - Carp: Oral bioavailability is estimated at 3.7%–9.0%, depending on the dose[1] - Human: Oral absorption varies considerably due to chelation with divalent cations (25%–58%)[3] - Distribution: - Carp: Highest concentrations are found in the liver and kidneys, with residual amounts in muscle increasing with dose[1] - Human: Primarily distributed in bones, teeth, and skin[3] - Metabolism: - Carp: Primarily metabolized by hepatic cytochrome P450 enzymes[1] - Human: Partially metabolized in the liver to inactive conjugates[3] - Excretion: - Carp: 60%–70% excreted unchanged in urine and bile[1] - Human: 40%–60% excreted in urine, 20%–30% in feces[3] - Half-life: - Carp: 12–24 hours in blood plasma [1] - Humans: 6–12 hours [3]

Effects During Pregnancy and Lactation
◉ Overview of Drug Use During Lactation
Some reviews suggest that tetracyclines are contraindicated during lactation because they may cause staining of infant tooth enamel or deposition in bone. However, a careful review of existing literature indicates that short-term use of oxytetracycline during lactation is unlikely to cause harm because the drug concentration in breast milk is low, and the infant's absorption of the drug is inhibited by calcium in breast milk. Short-term use of oxytetracycline in lactating women is acceptable. As a theoretical precaution, prolonged or repeated use during lactation should be avoided. Monitor the infant for skin rashes and potential effects on the gut microbiota, such as diarrhea or candidiasis (thrush, diaper rash).
◉ Effects on Breastfed Infants
No adverse reactions were observed in breastfed infants receiving oral oxytetracycline 1.5 or 2 g/day for 3 consecutive days. The infant's age and degree of breastfeeding were not considered.
◉ Effects on Lactation and Breast Milk
No relevant published information was found as of the revision date.

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Interactions
Concurrent administration of ferrous sulfate reduces the body's absorption of oxytetracycline and leads to a significant decrease in serum oxytetracycline concentration. Concurrent consumption of milk reduces oxytetracycline absorption by approximately 50%... . ...

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Non-human toxicity values
Swiss mouse oral LD50 7200 mg/kg /hydroxytetracycline hydrochloride/

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- Acute toxicity: - Carp: LD50 > 5000 mg/kg (oral) [1] - Human: LD50 has not been determined; overdose may cause nausea, vomiting and hepatotoxicity [3] - Chronic toxicity: - Carp: Adding 300 mg/kg to feed causes significant hepatic and renal oxidative stress [1] - Human: Long-term use may cause photosensitivity, esophageal ulcers and tooth discoloration in children [3] - Drug interactions: - Chelates with calcium, iron and magnesium, reducing absorption [3] - Inhibits cytochrome P450 enzymes, increasing warfarin and digoxin levels [3]

[1]. Transferability of oxytetracycline (OTC) from feed to carp muscle and evaluation of the antibiotic effects on antioxidant systems in liver and kidney. Fish Physiol Biochem, 2014 Aug;40(4):1055-68.

[2]. Oxytetracycline biosynthesis. J Biol Chem. 2010 Sep 3;285(36):27509-15.

[3]. A New Treatment Method for Herpes Simplex Virus Type 1-related Skin Lesions. Scientific & Academic. 2019; 8(1): 6-8.

Depending on state or federal labeling requirements, oxytetracycline (oral) may cause developmental toxicity. Oxytetracycline is a tetracycline antibiotic used to treat infections caused by a variety of Gram-positive and Gram-negative bacteria, including Mycoplasma pneumoniae, Pasteurella multocida, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae. It has multiple actions, including antibacterial activity, protein synthesis inhibition, antimicrobial activity, anti-inflammatory activity, and bacterial metabolite activity. It is a zwitterionic tautomer of oxytetracycline. An anhydrous oxytetracycline is a tetracycline antibacterial agent. Oxytetracycline has been reported to be found in Streptomyces anthocyanicus, Streptomyces varsoviensis, and other microorganisms with relevant data.
Oxytetracycline, a tetracycline analog isolated from the actinomycete Streptomyces rimosus, is widely used for a variety of clinical diseases.
Drug Indications

Oxytetracycline is indicated for the treatment of infections caused by a variety of Gram-positive and Gram-negative bacteria, including Mycoplasma pneumoniae, Pasteurella multocida, Escherichia coli, Haemophilus influenzae (respiratory tract infection), and Streptococcus pneumoniae.
Mechanism of Action

Oxytetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit, preventing aminoacyl-tRNA from binding to the A site of the ribosome. This binding is reversible. Oxytetracycline is lipophilic and can easily cross the cell membrane or passively diffuse through porin channels on the bacterial membrane.
Tetracycline drugs inhibit bacterial protein synthesis by binding to the bacterial 30S ribosome, preventing aminoacyl-tRNA from binding to the receptor (A) site on the mRNA-ribosome complex. They passively diffuse into Gram-negative bacteria through hydrophilic channels formed by porins in the outer cell membrane, or actively transport via an energy-dependent system that pumps all tetracyclines into the cytoplasmic membrane. Although the mechanisms by which these drugs penetrate Gram-positive bacteria are poorly understood, this process also requires energy. At high concentrations, these compounds inhibit protein synthesis in mammalian cells. However, because mammalian cells lack the active transport systems present in bacteria and have lower sensitivity to ribosome targets, tetracyclines exhibit selective activity against bacteria. Tetracycline antibiotics… may exert neuromuscular blocking effects through chelation of Ca²⁺. /Tetracyclines/

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Therapeutic Uses
MeSH Title: Antibacterial Agents
Antibiotics, Tetracyclines
...broad-spectrum antibacterial activity against Gram-positive and Gram-negative bacteria...against some microorganisms naturally insensitive to many chemotherapeutic agents, such as Rickettsia, Mycoplasma, Chlamydia, lymphogranuloma venereum, psittacosis, inclusion conjunctivitis and trachoma pathogens, and amoebae. /Tetracyclines/
Tetracyclines are active against a wide variety of aerobic and anaerobic Gram-positive and Gram-negative bacteria. They are also effective against some microorganisms resistant to cell wall-active antibacterial agents, such as Rickettsia, Coxsella burgdorferi, Mycoplasma pneumoniae, Chlamydia spp., Legionella spp., Ureaplasma, some atypical mycobacteria, and Plasmodium spp. They are ineffective against fungi. Tetracyclines
For more complete data on the therapeutic uses of oxytetracyclines (28 in total), please visit the HSDB records page.

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Drug Warnings
While individual differences have not shown significant variations except in a few extreme cases, some oxytetracycline preparations have been shown to be ineffective against generic drugs.
Food, milk, non-systemic antacids, and iron supplements can interfere with oral absorption.
…Ineffective against any true virus, yeast, or fungus. Tetracyclines
Due to the high risk of sensitization, topical application is best avoided, except for ophthalmic application…Intrathecal injection is absolutely prohibited. /Tetracyclines/
For more complete data on drug warnings for oxytetracyclines (38 in total), please visit the HSDB records page.

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Pharmacodynamics
Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against a variety of infections. It was the second tetracycline to be discovered. Like other tetracyclines, oxytetracycline is used to treat many common and rare infections. Due to its better absorption properties, oxytetracycline is superior to tetracycline in treating moderate to severe acne, but if the condition does not improve after 3 months, other alternative drugs should be sought.

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- Background:- Oxytetracycline is a broad-spectrum antibiotic derived from Streptomyces rimosus and is used in veterinary and human medicine[1][3]- Mechanism of action:- Antibacterial: Inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit[1]- Antiviral: Interferes with the synthesis of HSV-1 envelope glycoprotein[3]- Indications:- Veterinary: Bacterial infections in fish and livestock[1]- Human: Respiratory and urinary tract infections; acne; HSV-1 skin lesions[3]- Regulatory status:- Approved for veterinary use in many countries; its use in humans is restricted due to resistance[3]

460.148

C, 57.39; H, 5.25; N, 6.08; O, 31.27

79-57-2

Oxytetracycline hydrochloride;2058-46-0;Oxytetracycline dihydrate;6153-64-6;Oxytetracycline calcium;7179-50-2

54675779

Light yellow to yellow solid powder

1.7±0.1 g/cm3

727.8±60.0 °C at 760 mmHg

183 °C

394.0±32.9 °C

0.0±2.5 mmHg at 25°C

1.762

0.56

7

10

2

33

1000

6

O[C@@]12C(=O)C(C(=O)N)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]([C@@H]1[C@@](O)(C)C3C=CC=C(C=3C(=O)C1=C2O)O)O

OWFJMIVZYSDULZ-PXOLEDIWSA-N

InChI=1S/C22H24N2O9/c1-21(32)7-5-4-6-8(25)9(7)15(26)10-12(21)17(28)13-14(24(2)3)16(27)11(20(23)31)19(30)22(13,33)18(10)29/h4-6,12-14,17,25-26,28,30,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1

(4S,4aR,5S,5aR,6S,12aR)-4-(dimethylamino)-1,5,6,10,11,12a-hexahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide

oxytetracycline; 79-57-2; Terramycin; RefChem:932744; Lidocaine hydrochloride; oxytetracycline; (4S,4aR,5S,5aR,6S,12aR)-2-carbamoyl-4-(dimethylazaniumyl)-5,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracen-1-olate; ...; 79-57-2;Oxyterracine; Oxytetracyclin; Oxymycin; Terrafungine; Oxyterracin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ≥ 50 mg/mL (~108.59 mM)
H2O : ~0.67 mg/mL (~1.46 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.43 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 25.0 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: ≥ 2.5 mg/mL (5.43 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 25.0 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.43 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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