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Identification
Name Doxycycline
Accession Number DB00254 (APRD00597)
Type small molecule
Groups approved
Description

A synthetic tetracycline derivative with similar antimicrobial activity. Animal studies suggest that it may cause less tooth staining than other tetracyclines. It is used in some areas for the treatment of chloroquine-resistant falciparum malaria (malaria, falciparum). [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Doxcycline anhydrous
  • Doxycycline Hyclate
  • Doxycycline Monohydrate
  • Doxytetracycline
Brand names
  • Alti-Doxycycline
  • Apo-Doxy
  • Atridox
  • Doryx
  • Doxy 100
  • Doxy-Caps
  • Doxy-Lemmon
  • Doxychel
  • Doxychel Hyclate
  • Doxycin
  • Doxylin
  • Doxytec
  • Jenacyclin
  • Monodox
  • Novo-Doxylin
  • Nu-Doxycycline
  • Oracea
  • Periostat
  • Supracyclin
  • Vibra-Tabs
  • Vibramycin
Brand name mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Antimalarials
  • Tetracyclines
CAS number 564-25-0
Weight Average: 444.4346
Monoisotopic: 444.153265754
Chemical Formula C22H24N2O8
InChI Key InChIKey=JBIWCJUYHHGXTC-AKNGSSGZSA-N
InChI
InChI=1S/C22H24N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31)/t7-,10+,14+,15-,17-,22-/m0/s1
Plain Text
IUPAC Name
(4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12[C@@H](C)C3=CC=CC(O)=C3C(=O)C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]1([H])[C@H]2O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes
  • Tetracyclines
Substructures
  • Tetracyclines
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Aromatic compounds
  • Cinnamaldehydes
  • Ketenes and Derivatives
  • Phenyl Esters
  • Enols
  • Ketones
Pharmacology
Indication Doxycycline is indicated for use in respiratory tract infections caused by Mycoplasma pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae, Legionella spp., or Klebsiella spp. It is also used for prophylaxis of malaria. Doxycycline is indicated for a variety of bacterial infections, from Mycobacterium fortuitum and M. marinum, to susceptible E. coli and Brucella spp. It can be used as an alternative to treating plague, tetanus, Campylobacter fetus
Pharmacodynamics Doxycycline, a long-acting tetracycline derived from oxytetracycline, is used to inhibit bacterial protein synthesis and treat non-gonococcal urethritis and cervicitis, exacerbations of bronchitis in patients with COPD, and adult periodontitis.
Mechanism of action Doxycycline, like minocycline, is lipophilic and can pass through the lipid bilayer of bacteria. Doxycycline reversibly binds to the 30 S ribosomal subunits and possibly the 50S ribosomal subunit(s), blocking the binding of aminoacyl tRNA to the mRNA and inhibiting bacterial protein synthesis. Doxycycline prevents the normal function of the apicoplast of Plasmodium falciparum, a malaria causing organism.
Absorption Completely absorbed following oral administration.
Volume of distribution Not Available
Protein binding >90%
Metabolism

Hepatic
Route of elimination They are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
Half life 18-22 hours
Clearance Not Available
Toxicity Symptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD50=262 mg/kg (I.P. in rat).
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Pathway Name SMPDB ID
Smp00291 Doxycycline Pathway SMP00291
Pharmacoeconomics
Manufacturers
  • Mylan pharmaceuticals inc
  • Par pharmaceutical inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Watson laboratories inc
  • Watson pharmaceuticals inc
  • Galderma laboratories lp
  • Rachelle laboratories inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Pfizer laboratories div pfizer inc
  • Lannett holdings inc
  • Mutual pharmaceutical co inc
  • Pliva inc
  • Mayne pharma international faulding pharm
  • Warner chilcott bermuda ltd
  • Medicis pharmaceutical corp
  • Halsey drug co inc
  • Heather drug co inc
  • Interpharm inc
  • Private formulations inc
  • Ranbaxy pharmaceuticals inc
  • Superpharm corp
  • Warner chilcott div warner lambert co
  • West ward pharmaceutical corp
  • Teva pharmaceuticals usa inc
  • Collagenex inc
  • App pharmaceuticals llc
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Tolmar inc
  • Corepharma llc
  • Larken laboratories inc
  • Mutual pharmacal co
  • Truxton inc
  • Vintage pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Gel, metered Periodontal
Tablet Oral
Prices
Unit description Cost Unit
Vibramycin 25 mg/5ml Suspension 60ml Bottle 36.29 USD bottle
Adoxa pak 1-150 mg tablet 19.93 USD tablet
Doryx 150 mg Enteric Coated Tabs 17.51 USD tab
Doryx dr 150 mg tablet 16.83 USD tablet
Doxycycline hyc 100 mg vial 14.16 USD vial
Adoxa 100 mg tablet 13.86 USD tablet
Monodox 100 mg capsule 13.46 USD capsule
Adoxa 75 mg tablet 12.77 USD tablet
Oracea 40 mg Delayed Release Capsule 12.44 USD capsule
Oracea 40 mg capsule 11.96 USD capsule
Avidoxy 100 mg tablet 11.52 USD tablet
Monodox 75 mg capsule 11.02 USD capsule
Doryx 100 mg Enteric Coated Tabs 10.31 USD tab
Doryx dr 100 mg tablet 9.91 USD tablet
Adoxa pak 1-100 mg tablet 9.88 USD tablet
Doxycycline Monohydrate 150 mg tablet 9.51 USD tablet
Adoxa 50 mg tablet 9.29 USD tablet
Doxycycline mono 150 mg tablet 9.13 USD tablet
Doryx 75 mg Enteric Coated Tabs 8.76 USD tab
Doryx dr 75 mg tablet 8.42 USD tablet
Vibramycin 100 mg capsule 6.67 USD capsule
Vibra-tabs 100 mg tablet 6.67 USD tablet
Monodox 50 mg capsule 6.0 USD capsule
Doxycycline mono 100 mg tablet 5.98 USD tablet
Periostat 20 mg tablet 5.75 USD tablet
Doxycycline mono 75 mg tablet 5.74 USD tablet
Doxycycline Monohydrate 100 mg tablet 5.12 USD tablet
Doxycycline mono 50 mg tablet 4.17 USD tablet
Doxycycline Monohydrate 50 mg tablet 3.0 USD tablet
Doxycycline hyclate powder 2.56 USD g
Vibramycin 50 mg capsule 2.41 USD capsule
Doxycycline Monohydrate 100 mg capsule 2.22 USD capsule
Vibramycin 100 mg Capsule 1.91 USD capsule
Doxycycline Monohydrate 50 mg capsule 1.51 USD capsule
Doxycycline hyclate 100 mg tablet 1.28 USD tablet
Doxycycline hyclate 20 mg tablet 1.28 USD tablet
Doxycycline Hyclate 100 mg capsule 1.18 USD capsule
Doxycycline Hyclate 50 mg capsule 0.76 USD capsule
Vibramycin 50 mg/5ml Syrup 0.67 USD ml
Vibramycin 50 mg/5 ml syrup 0.64 USD ml
Apo-Doxy 100 mg Capsule 0.61 USD capsule
Apo-Doxy 100 mg Tablet 0.61 USD tablet
Doxycin 100 mg Capsule 0.61 USD capsule
Doxycin 100 mg Tablet 0.61 USD tablet
Novo-Doxylin 100 mg Capsule 0.61 USD capsule
Novo-Doxylin 100 mg Tablet 0.61 USD tablet
Nu-Doxycycline 100 mg Capsule 0.61 USD capsule
Pms-Doxycycline 100 mg Capsule 0.61 USD capsule
Pms-Doxycycline 100 mg Tablet 0.61 USD tablet
Patents
Country Patent Number Approved Expires
United States 7749532 2007-12-19 2027-12-19
United States 5789395 1996-08-30 2016-08-30
Properties
State solid
Melting point 201 oC
Experimental Properties
Property Value Source
water solubility 630 mg/L PhysProp
logP -0.2 PhysProp
logS -2.87 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 6.30e-01 g/l ALOGPS
logP -0.72 ALOGPS
logP -3.37 ChemAxon Molconvert
logS -2.85 ALOGPS
pKa 4.79 ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 6 ChemAxon Molconvert
polar surface area 181.62 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 113.89 ChemAxon Molconvert
polarizability 42.88 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ: Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob Agents Chemother. 2006 Sep;50(9):3124-31. Pubmed
  2. Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Buttner DW: Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production. Med Microbiol Immunol. 2003 Nov;192(4):211-6. Epub 2003 Mar 5. Pubmed
  3. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A: Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005 Jun 18-24;365(9477):2116-21. Pubmed
External Links
Resource Link
KEGG Compound C06973 Link_out
PubChem Compound 5281011 Link_out
PubChem Substance 46506491 Link_out
ChemSpider 4444486 Link_out
BindingDB 50041429 Link_out
ChEBI 50845 Link_out
ChEMBL 50845 Link_out
Therapeutic Targets Database DAP001371 Link_out
PharmGKB PA449415 Link_out
Drug Product Database 742562 Link_out
RxList http://www.rxlist.com/cgi/generic/doxycyc.htm Link_out
Drugs.com http://www.drugs.com/doxycycline.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Doxycycline Link_out
ATC Codes
  • A01AB22
  • J01AA02
AHFS Codes
  • 08:12.24
  • 52:04.04
PDB Entries
FDA label show (48.1 KB)
MSDS show (73.4 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminum salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take with a full glass of water Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Targets

1. 30S ribosomal protein S9

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P0A7X3 Link_out
Gene: rpsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed

2. 30S ribosomal protein S4

Pharmacological action: yes
Actions: inhibitor

Also functions as a rho-dependent antiterminator of rRNA transcription, increasing the synthesis of rRNA under conditions of excess protein, allowing a more rapid return to homeostasis. Binds directly to RNA polymerase

Organism class: bacterial
UniProt ID: P0A7V8 Link_out
Gene: rpsD
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed

3. 16S rRNA

Pharmacological action: yes
Actions: inhibitor

In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.

Gene Sequence: FASTA

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
  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
  3. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. Pubmed
  4. Kumar S, Kutlin A, Roblin P, Kohlhoff S, Bodetti T, Timms P, Hammerschlag MR: Isolation and antimicrobial susceptibilities of Chlamydial isolates from Western barred bandicoots. J Clin Microbiol. 2007 Feb;45(2):392-4. Epub 2006 Nov 22. Pubmed
  5. Ross JI, Eady EA, Cove JH, Cunliffe WJ: 16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium. Antimicrob Agents Chemother. 1998 Jul;42(7):1702-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  2. Zhao XJ, Ishizaki T: A further interaction study of quinine with clinically important drugs by human liver microsomes: determinations of inhibition constant (Ki) and type of inhibition. Eur J Drug Metab Pharmacokinet. 1999 Jul-Sep;24(3):272-8. Pubmed
Transporters

1. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Solute carrier family 22 member 8

Actions: inhibitor

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, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

3. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on July 25, 2011 18:54

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.