Chemicals / Complex Chemical Agents/ Chemical:

Doxycycline (with special reference to Lagomorphs, Ferrets and Great Apes)

INFORMATION AVAILABLE

GENERAL CHEMICAL INFORMATION THERAPEUTIC INFORMATION [DOSE, FREQUENCY & ROUTE]

NUTRITIONAL INFORMATION

TOXICITY INFORMATION ENVIRONMENTAL INFORMATION
Information in this page has been entered to support the current volumes of Wildpro and further information will be added as new volumes are completed. This page is not intended to substitute for the manufacturer's data sheet and the information is not yet complete for all species, or for all contra-indications etc.

CAUTION: Before any pharmaceutical product is used, the manufacturer's data sheet, containing information on uses, dosage and administration, contra-indications, warnings etc., should always be consulted. It is important to remember that licensing of pharmaceutical products for use in a particular species/condition, as well as mandatory meat and milk withdrawal times for food-producing animals, varies between countries and changes with time. Withdrawal times also may vary between different pharmaceutical formulations and depending on route of administration. In the EU, the prescription cascade must be followed (see LCofC1.2H and W564.Apr05.w1); note that specific restrictions apply for food-producing animals. In the USA, FARAD may be consulted regarding residues and meat and milk withdrawal times.

General Chemical Information

Summary 
Broad-spectrum bacteriostatic tetracycline antibiotic. (B135.44.w44)

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Names and Formulae
Type Tetracycline B135.44.w44)
Alternative Names "Doryx; Doxy-caps; Monodox; Vibramycin; Vibra-tabs; 4-(Dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-2-naphthacenecarboxamide monohydrate; Doxylin." (W324)
Chemical Formula C22H26N2O9. (W324)
Chemical Structure (B135.44.w44)
Molecular Weight 462.4554. (W324)
Related Chemicals Other tetracyclines: tetracycline, oxytetracycline, chlortetracycline, demeclocycline, methacycline, minocycline. (B135.44.w44)

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Physical Properties / Chemistry
Appearance

Doxycycline: Crystalline, amphoteric. (B135.44.w44)

Melting point --
Boiling point --
Density Doxycycline hydrochloride: more soluble than doxycycline. (B135.44.w44)
Water solubility --
Other solubility --
Acid/Base Doxycycline hydrochloride solution: acidic. (B135.44.w44)

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Pharmacology & General Information
Pharmacology
  • Enters microorganisms partially by passive diffusion, partly by energy-dependent active transport. Susceptible cells concentrate the drug. (B135.44.w44)
  • With the cell tetracyclines bind reversibly to receptors on the 30S ribosomal subunit, blocking the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex and thus effectively preventing addition of new amino acids to the peptide chain, therefore inhibiting protein synthesis. (B135.44.w44)
Storage / Stability --
Legal Category (In UK) --

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References

Associated Techniques

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ORGANISATIONS

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ELECTRONIC LIBRARY
(Further Reading)
Click image for full contents list of ELECTRONIC LIBRARY

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Authors Debra Bourne (V.w5)
Referees Suzanne I. Boardman (V.w6); Becki Lawson (V.w26)

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Therapeutic Information

Uses/Indications
Activity
Appropriate Use
  • Doxycycline-sensitive infections. (B201)
  • Tetracycline-sensitive infections in azotaemic individuals. (B263)
  • Considered by some to be the "drug of choice" for oral medication of birds with psittacosis. (B263)
Limitations
  • Most populations of susceptible organisms contain small numbers of resistant organisms, lacking the active transport mechanism across the cell membrane, or lacking passive permeability to tetracyclines. (B135.44.w44)
  • Highly resistant types of Gram-negative bacteria such as Pseudomonas spp., Proteus spp. and coliforms have been selected, greatly reducing the usefulness of tetracyclines. (B135.44.w44)
  • Tetracycline resistance is generally plasmid-transmitted and as the genes for tetracycline resistance are closely associated with those for resistance to other drugs such as aminoglycosides and sulphonamides plasmids often transmit resistance to multiple drug groups. (B135.44.w44)
Notes --

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Pharmacokinetics and Drug Interactions
Absorption /Bioavailability
  • Irregular absorption from the gastro-intestinal tract: a percentage of orally-administered tetracycline will remain in the gut lumen, modify intestinal flora and be excreted in the faeces. (B135.44.w44)
  • 90-100% of orally administered doxycycline is absorbed (human). (B135.44.w44)
  • Absorbed mainly from the upper small intestine. (B135.44.w44)
  • Better absorption in the absence of food. (B135.44.w44)
  • Absorption of tetracyclines is impaired by chelation with divalent cations Ca2+, Mg2+, Fe2+ and with AL 3+, particularly in milk or antacids.(B135.44.w44)
    • Absorption of doxycycline is less affected by milk than are the other tetracyclines. (B201)
  • Absorption is impaired by alkaline pH. (B135.44.w44)
  • Serum half-life in dogs approximately 10-12 hours. (B263)
Distribution
  • Wide distribution in tissues and body fluids. (B135.44.w44)
  • Good penetration into bronchial secretions and prostatic fluids. (B201)
  • Only low concentrations in cerebrospinal fluid. (B135.44.w44)
  • Human: oral administration of 500mg every six hours results in peak blood levels of 2-4 g/ml. (B135.44.w44)
  • Deposited in developing teeth; in puppies kittens, following direct dosing or dosing of the mother in late pregnancy, may result in discoloured teeth and enamel defects in the temporary teeth. (B201)
Plasma Protein binding / Storage
  • Tetracyclines are 40-80% protein-bound. (B135.44.w44)
  • Humans: 25-93% plasma protein-bound (approx.). (B263)
  • Dogs: 75-86%. (B263)
  • Cattle, pigs: about 93%. (B263)
  • Cats: higher than in dogs. (B263)
Elimination Route
  • Tetracyclines are mainly eliminated in bile and urine. (B135.44.w44)
  • Tetracycline have ten times higher concentration in bile than in serum, partial reabsorption (enterohepatic circulation). (B135.44.w44)
  • 10-50% of tetracyclines are excreted, primarily by glomerular filtration, in urine. (B135.44.w44)
  • 10-40% of tetracyclines are excreted in faeces. (B135.44.w44)
  • Doxycycline does not require renal excretion and does not accumulate significantly in individuals with renal failure. (B135.44.w44); safe for use in individuals with renal impairment. (B201)
  • Doxycycline is excreted in the faeces by a non-biliary route (thought to involve partial inactivation by chelation in the intestine, then excretion into the intestinal lumen). This may be the excretion route for 75% of a given dose in dogs. (B263)
  • In dogs, biliary excretion may be less than 5% and renal excretion only about 25%. (B263)
Elimination half-life / Clearance Rate
  • Renal clearance of oxytetracycline (Human): 16 ml/minute. (B135.44.w44)

Clearance rate:

  • Dogs: 1.7 ml/kg/minute. (B263)
  • Calves: similar to dogs. (B263)
Drug Interactions
  • Orally administered tetracycline may chelate divalent or trivalent cations: absorption of the tetracycline/other preparation may be decreased: oral administration should be separated by at least one to two hours. (B263). The affinity of doxycycline for calcium ions is relatively low. (B263)
  • Decreased adsorption of orally administered tetracyclines in the presence of oral iron products: give iron salts at least three hours before or two hours after the tetracycline. (B263)
  • Decreased absorption of orally administered tetracyclines may occur if given together with oral sodium bicarbonate, kaolin, pectin or bismuth subsalicylate. (B263)
  • Tetracyclines, being bacteriostatic, may interfere with the bactericidal effect of beta-lactam antibiotics (penicillins and cephalosporins) and aminoglycosides (some controversy regarding the clinical significance). (B263)
  • Tetracyclines may, in a small proportion of human patients, increase digoxin bioavailability, leading to digoxin toxicity: this effect may persist for months after the tetracycline administration is discontinued. (B263).
  • Tetracyclines may depress the activity of plasma prothrombin: individuals receiving anticoagulants such as warfarin may require adjustment of their anticoagulant dose. (B263)
  • Reportedly (not yet confirmed by controlled studies), tetracyclines may reduce the insulin requirements of diabetic individuals. (B263)
  • May increase the nephrotoxic effects of methoxyflurane. (B263)
  • Concurrent use with theophylline may lead to increased gastro-intestinal side effects. (B263)

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Administration
Formulations available In UK:
Doses / Administration Routes / Frequencies

Use of Drugs (Medication):

  • Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
  • Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
  • Consideration should be given to relevant legislation regarding the use of drugs.
  • In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).

In cats and dogs: 

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

  • 2.5 - 4.0 mg/kg orally every 24 hours. (B546)
  • 2.5 mg/kg orally every 12 hours. (B548.w8)
  • 4 mg/kg orally every 24 hours. (B548.w8)
  • 2.5 mg/kg orally every 12 hours. (B601.15.w15)
  • 2.5 mg/kg orally every 12 hours. (B602.41.w41)
  • 4 mg/kg every 12 - 24 hours. (B603.5.w5)
    • Note: Tetracyclines are broad-spectrum, including activity against Pasteurella spp. and against many anaerobes, with good tissue penetration including of bones and teeth. If given in drinking water, water intake may be decreased and absorption is low. (B603.5.w5)

In Ferrets - Mustela putorius fero - Ferret:

  • "Drug as paste useful if prepared to be empirical." (B626.App.w22)

Great Apes

  • 5.0 mg/kg orally every 12 hours for one day then 2.5 mg/kg every 24 hours. For the treatment of Entamoeba and Balantidium infections. (B336.39.w39)
  • Adult Pan troglodytes - Chimpanzee: 2 - 5 mg/kg orally twice daily. (W768.Jun2012.w1)
  • Primates: 5 mg/kg orally twice daily for the first 24 hours, then 2.5 mg/kg orally twice daily thereafter. As an antibiotic. (D425.3.15.w3o)
  • Primates: 20 mg/kg orally three times daily five to ten days. In the treatment of Balantidium coli Infection in Bonobos.(D425.3.15.w3o)

BIRDS

In pigeons and cage birds: 

  • 15 mg/kg bodyweight daily. Dissolve one sachet (260 mg) in two litres of deionised or distilled water. For birds such as parakeets which have a low daily water intake dissolve one sachet in 0.5 litres of distilled or deionised water. Use for five days, or longer for severe infections. "For the treatment of the respiratory tract ornithosis and psittacosis [Chlamydiosis - Psittacosis in Birds (with special reference to Waterfowl)] ocular infections caused by Chlamydia psittaci or Mycoplasma in pigeons and cage birds." (B266)
  • "During the [pigeon] racing season, Ornicure can be used prophylactically during 2 consecutive days out of 7 weekly." (B266)
Monitoring parameters --

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Withdrawal period / Withholding time
Notes Before the use of any pharmaceutical product in food-producing animals the label instructions for the product should be consulted regarding withdrawal requirements.

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Toxic Information

Toxic effects of Pharmaceutical Products
Contraindications / Precautions
  • Caution in using in horses as stressed horses given parenteral or oral tetracyclines may develop severe, sometimes fatal, enterocolitis. (B201) Doxycycline is particularly likely to cause enterocolitis in horses.  (B201)
  • Contra-indicated for use in pregnant animals. (B201); Contra-indicated in the last half of pregnancy unless the benefits "outweigh the fetal risks", due to risk of discolouration of teeth and retardation of skeletal growth: these effects may be less likely with doxycycline than with tetracycline or oxytetracycline. (B263)
  • Avoid use during the reproductive period of birds. (B201)
  • Pigeons under treatment should not participate in races (manufacturers recommendation). (B201)
Adverse Effects / Side Effects / Warnings
  • Dogs and cats: nausea and vomiting; these may be reduced by administering the drug with food. (B263)
  • Cats: oesophageal strictures following oral administration: if a pill is given this should be followed by at least six ml of water. (B263)
  • Long-term use may result in superinfection (overgrowth) with non-susceptible bacteria or fungi. (B263)
  • In horses, intravenous administration has resulted in cardiac arrhythmias, collapse and death. (B263)
  • In humans, tetracyclines have been associated with photosensitivity reactions. (B263)
  • In humans rare side effects include hepatotoxicity and blood dyscrasias. (B263)
Operator Warnings Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
Overdose / Acute Toxicity
  • Oral overdoses are most likely to result in gastrointestinal disturbances such as vomiting, anorexia and/or diarrhoea. (B263)
    • Effects of overdose may be reduced by oral administration of divalent or trivalent cations to chelate the drug. (B263)
  • Severe and fatal toxicity may be seen in horses (see above). (B263)

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Detailed Toxicological Information
Classification --
Acute Toxicity --
Chronic Toxicity --
Reproductive effects --
Teratogenic effects --
Mutagenic effects --
Carcinogenic effects

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Organ toxicity --
Bird Toxicity --
Aquatic organism activity --
Other organism toxicity --

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Nutrient Information

Nutritional Data
Sources --
Biological Use --
Recommended Daily Allowance / Recommended level in food --
Stability in food (Storage time) --
Interactions --

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External / Environmental Information

External / Environmental Uses
Use --
Formulation --
Application method --
Application Concentration --
Persistence of Effect / Frequency of Application --

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Effects on the Environment
Effects in the aquatic environment

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Effects on land --

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Persistence in the Environment
Breakdown in soil and groundwater

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Breakdown in water --
Breakdown in vegetation --

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