Identification

Name
Oxytetracycline
Accession Number
DB00595  (APRD00019)
Type
Small Molecule
Groups
Approved, Investigational, Vet Approved
Description

A tetracycline analog isolated from the actinomycete streptomyces rimosus and used in a wide variety of clinical conditions.

Structure
Thumb
Synonyms
  • 5-Hydroxytetracycline
  • Embryostat
  • Hydroxytetracyclinum
  • Mepatar
  • Oxitetraciclina
  • Oxyterracin
  • Oxyterracine
  • Oxytetracyclin
  • Oxytétracycline
  • Oxytetracycline (anhydrous)
  • Oxytetracycline amphoteric
  • Oxytetracyclinum
Product Ingredients
IngredientUNIICASInChI Key
Oxytetracycline calciumC8MRZ07FDV13303-91-8KIPLYOUQVMMOHB-MXWBXKMOSA-L
Oxytetracycline dihydrateX20I9EN9556153-64-6SRRPEXWCHWWJOC-JEKSYDDFSA-N
Oxytetracycline hydrochloride4U7K4N52ZM2058-46-0UBDNTYUBJLXUNN-IFLJXUKPSA-N
Oxytetracycline mono-alkyl trimethyl ammoniumNot AvailableNot AvailableNot applicable
Oxytetracycline monocalciumM90SJ24J2X7179-50-2QJHKFWPAQRFQBG-IFLJXUKPSA-L
International/Other Brands
Adamycin (Teva) / Anglocycline (Anglopak) / Corsamycin (Corsa Industries) / Oxacin (Doctor's Chemical Works) / Oxypan (Adcock Ingram Pharmaceuticals) / Oxyterracyna (Chema) / Terrados (Pfizer) / Terramycin (Pfizer) / Tetran (Wagner Pharmafax) / Tetrasona (Medifarma)
Categories
UNII
SLF0D9077S
CAS number
79-57-2
Weight
Average: 460.434
Monoisotopic: 460.148180376
Chemical Formula
C22H24N2O9
InChI Key
IWVCMVBTMGNXQD-PXOLEDIWSA-N
InChI
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/h4-6,12-14,17,25,27-29,32-33H,1-3H3,(H2,23,31)/t12-,13-,14+,17+,21-,22+/m1/s1
IUPAC Name
(4S,4aR,5S,5aR,6S,12aS)-4-(dimethylamino)-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][[email protected]@]12[[email protected]@H](O)[[email protected]@]3([H])C(C(=O)C4=C(O)C=CC=C4[[email protected]@]3(C)O)=C(O)[[email protected]]1(O)C(=O)C(C(N)=O)=C(O)[[email protected]]2N(C)C

Pharmacology

Indication

Oxytetracycline is indicated for treatment of infections caused by a variety of Gram positive and Gram negative microorganisms including Mycoplasma pneumoniae, Pasteurella pestis, Escherichia coli, Haemophilus influenzae (respiratory infections), and Diplococcus pneumoniae.

Structured Indications
Not Available
Pharmacodynamics

Oxytetracycline is known as a broad-spectrum antibiotic due to its activity against such a wide range of infections. It was the second of the tetracyclines to be discovered. Oxytetracycline, like other tetracyclines, is used to treat many infections common and rare. Its better absorption profile makes it preferable to tetracycline for moderately severe acne, but alternatives sould be sought if no improvement occurs by 3 months.

Mechanism of action

Oxytetracycline inhibits cell growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Oxytetracycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane.

TargetActionsOrganism
A30S ribosomal protein S9
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S4
inhibitor
Escherichia coli (strain K12)
U16S rRNA
inhibitor
Enteric bacteria and other eubacteria
Absorption

Readily absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Adverse effects may include stomach or bowel upsets and rarely allergic reactions. Very rarely severe headache and vision problems may be signs of dangerous intracranial hypertenion.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Oxytetracycline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Oxytetracycline.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Oxytetracycline.Approved
Food Interactions
Not Available

References

Synthesis Reference

Janos Balint, Laszlo Cseke, Ferenc Fabian, Lajos Kun, Miklos Szarvas, "Process for the preparation of an oxytetracycline-calcium silicate complex salt from fermentation broth." U.S. Patent US4584135, issued April, 1951.

US4584135
General References
Not Available
External Links
KEGG Compound
C06624
PubChem Compound
54675779
PubChem Substance
46507025
ChemSpider
10482174
ChEBI
27701
ChEMBL
CHEMBL1517
Therapeutic Targets Database
DAP000401
PharmGKB
PA450757
HET
OTC
RxList
RxList Drug Page
Wikipedia
Oxytetracycline
ATC Codes
J01AA56 — Oxytetracycline, combinationsS01AA04 — OxytetracyclineJ01AA20 — Combinations of tetracyclinesJ01AA06 — OxytetracyclineD06AA03 — OxytetracyclineG01AA07 — Oxytetracycline
PDB Entries
2xpw
MSDS
Download (73.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1, 2RecruitingTreatmentLung Cancers1
3Unknown StatusTreatmentAcne Vulgaris II or III Degree / Furuncle1
Not AvailableCompletedTreatmentKeratoconjunctivitis Sicca1

Pharmacoeconomics

Manufacturers
  • Pfizer laboratories div pfizer inc
  • John j ferrante
  • Impax laboratories inc
  • Proter laboratory spa
  • Purepac pharmaceutical co
  • West ward pharmaceutical corp
Packagers
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Terramycin-polymyx eye ointm3.85USD g
Oxytetracycline hcl powder3.59USD g
Terramycin 250 mg/2 ml ampul2.22USD ml
Terramycin im 100 mg/2 ml amp1.24USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184.5 °CPhysProp
water solubility313 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.90SANGSTER (1994)
logS-3.14ADME Research, USCD
pKa3.27 (at 25 °C)KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility1.4 mg/mLALOGPS
logP-0.99ALOGPS
logP-4.6ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)0.24ChemAxon
pKa (Strongest Basic)7.75ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area201.85 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity115.4 m3·mol-1ChemAxon
Polarizability43.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.85
Blood Brain Barrier-0.9881
Caco-2 permeable-0.8706
P-glycoprotein substrateSubstrate0.699
P-glycoprotein inhibitor INon-inhibitor0.8038
P-glycoprotein inhibitor IINon-inhibitor0.8628
Renal organic cation transporterNon-inhibitor0.9562
CYP450 2C9 substrateNon-substrate0.8008
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6551
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.9144
CYP450 2D6 inhibitorNon-inhibitor0.9293
CYP450 2C19 inhibitorNon-inhibitor0.9099
CYP450 3A4 inhibitorNon-inhibitor0.8567
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8086
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8632
BiodegradationNot ready biodegradable0.9941
Rat acute toxicity2.3159 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9946
hERG inhibition (predictor II)Non-inhibitor0.7466
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Tetracyclines
Sub Class
Not Available
Direct Parent
Tetracyclines
Alternative Parents
Naphthacenes / Anthracenecarboxylic acids and derivatives / Tetralins / Aryl ketones / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Aralkylamines / Cyclohexenones / Tertiary alcohols / Vinylogous acids
show 9 more
Substituents
Tetracycline / Naphthacene / Tetracene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Aralkylamine
show 24 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:27701) / Linear tetracyclines, Antibiotic fungicides (C06624) / Linear tetracyclines (LMPK07000005)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome.
Gene Name
rpsI
Uniprot ID
P0A7X3
Uniprot Name
30S ribosomal protein S9
Molecular Weight
14856.105 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Aminov RI, Chee-Sanford JC, Garrigues N, Mehboob A, Mackie RI: Detection of tetracycline resistance genes by PCR methods. Methods Mol Biol. 2004;268:3-13. [PubMed:15156014]
  4. Skold SE: RNA-protein complexes identified by crosslinking of polysomes. Biochimie. 1981 Jan;63(1):53-60. [PubMed:6163479]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Translation repressor activity, nucleic acid binding
Specific Function
One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.With S5 and S12 plays an important role in trans...
Gene Name
rpsD
Uniprot ID
P0A7V8
Uniprot Name
30S ribosomal protein S4
Molecular Weight
23468.915 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Aminov RI, Chee-Sanford JC, Garrigues N, Mehboob A, Mackie RI: Detection of tetracycline resistance genes by PCR methods. Methods Mol Biol. 2004;268:3-13. [PubMed:15156014]
  4. Skold SE: RNA-protein complexes identified by crosslinking of polysomes. Biochimie. 1981 Jan;63(1):53-60. [PubMed:6163479]
3. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Unknown
Actions
Inhibitor
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Engemann CA, Adams L, Knapp CW, Graham DW: Disappearance of oxytetracycline resistance genes in aquatic systems. FEMS Microbiol Lett. 2006 Oct;263(2):176-82. [PubMed:16978353]
  4. Tsai HJ, Huang CW: Phenotypic and molecular characterization of isolates of Ornithobacterium rhinotracheale from chickens and pigeons in Taiwan. Avian Dis. 2006 Dec;50(4):502-7. [PubMed:17274285]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. [PubMed:11855680]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. [PubMed:11855680]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. [PubMed:11855680]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. [PubMed:11855680]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 17:28