DT-Web

DB00618 - Demeclocycline


Identification
Name Demeclocycline
Accession Number DB00618 (APRD00272)
Type small molecule
Description A tetracycline analog having a 7-chloro and a 6-methyl. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 464.853
Groups approved
Monoisotopic Weight 464.098643365
Pharmacology
Indication Used primarily to treat Lyme disease, acne, and bronchitis. Also indicated (but rarely used) to treat urinary tract infections, gum disease, malaria, and other bacterial infections such as gonorrhea and chlamydia. One of its other registered uses is the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective.
Mechanism of action Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.
Absorption Tetracyclines are readily absorbed.
Protein binding 41-50%
Biotransformation Hepatic
Route of elimination Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.
Toxicity Oral, rat: LD50 = 2372 mg/kg
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Acenocoumarol The tetracycline, demeclocycline, may increase the anticoagulant effect of acenocoumarol.
Acitretin Increased risk of intracranial hypertension
Aluminium Formation of non-absorbable complexes
Amoxicillin Possible antagonism of action
Ampicillin Possible antagonism of action
Anisindione The tetracycline, demeclocycline, may increase the anticoagulant effect of anisindione.
Attapulgite Formation of non-absorbable complexes
Azlocillin Possible antagonism of action
Aztreonam Possible antagonism of action
Bacampicillin Possible antagonism of action
Bexarotene Tetracycline derivatives like demeclocycline may enhance the adverse/toxic effect of Retinoic Acid Derivatives. Due to the risk of developing pseudotumor cerebri (also known as intracranial hypertension), avoid this combination of drugs if possible. If used concomitantly, monitor for evidence of this interaction (eg, dizziness, diplopia, headache).
Calcium Formation of non-absorbable complexes
Calcium Acetate Calcium salts such as calcium acetate may decrease the serum concentration of tetracycline derivatives such as demeoclocycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.
Calcium Chloride Calcium salts such as calcium chloride may decrease the serum concentration of tetracycline derivatives such as demeclocycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.
Carbenicillin Possible antagonism of action
Clavulanate Possible antagonism of action
Cloxacillin Possible antagonism of action
Colesevelam Bile acid sequestrants such as colesevelam may decrease the absorption of Tetracycline Derivatives. Monitor for decreased therapeutic effects of tetracycline derivatives if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction. The manufacturer of colesevelam suggests that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
Cyclacillin Possible antagonism of action
Dicloxacillin Possible antagonism of action
Dicumarol The tetracycline, demeclocycline, may increase the anticoagulant effect of dicumarol.
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Etretinate Increased risk of intracranial hypertension
Flucloxacillin Possible antagonism of action
Hetacillin Possible antagonism of action
Iron Formation of non-absorbable complexes
Iron Dextran Formation of non-absorbable complexes
Isotretinoin Increased risk of intracranial hypertension
Magnesium Formation of non-absorbable complexes
Magnesium oxide Formation of non-absorbable complexes
Mestranol This anti-infectious agent could decrease the effect of the oral contraceptive
Methoxyflurane The tetracycline, demeclocycline, may increase the renal toxicity of methoxyflurane.
Meticillin Possible antagonism of action
Mezlocillin Possible antagonism of action
Nafcillin Possible antagonism of action
Oxacillin Possible antagonism of action
Penicillin G Possible antagonism of action
Penicillin V Possible antagonism of action
Piperacillin Possible antagonism of action
Pivampicillin Possible antagonism of action
Pivmecillinam Possible antagonism of action
Tazobactam Possible antagonism of action
Ticarcillin Demeclocycline may reduce the effect of Ticarcillin by inhibiting bacterial growth. Ticarcillin exerts its effects on actively growing bacteria. To achieve synergism, Ticarcillin should be administered at least 2 hours prior to using Demeclocycline.
Tretinoin Demeclocycline may increase the adverse effects of oral Tretinoin. Increased risk of pseudotumour cerebri. Concurrent therapy should be avoided.
Warfarin The tetracycline, demeclocycline, may increase the anticoagulant effect of warfarin.
Zinc Formation of non-absorbable complexes
Food Interactions
  • Avoid milk and multivalent ions.
  • Take on an empty stomach.

Targets


30S ribosomal protein S9
Name 30S ribosomal protein S9
Gene Name rpsI
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1.079
30S ribosomal protein S4
Name 30S ribosomal protein S4
Gene Name rpsD
Pharmacological action yes
Actions inhibitor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
DTHybrid score 1

Predictions


Id Partner name Gene Name Score
6719 30S ribosomal protein S9 rpsI 1.079
6725 30S ribosomal protein S9 rpsI 1.079
6714 30S ribosomal protein S4 rpsD 1
1024 Solute carrier family 22 member 11 SLC22A11 0.0965
6142 Solute carrier family 22 member 8 SLC22A8 0.0812
1729 Solute carrier family 22 member 6 SLC22A6 0.0742
6208 30S ribosomal protein S13 rpsM 0.0567
6706 30S ribosomal protein S13 rpsM 0.0567
6143 Solute carrier family 22 member 7 SLC22A7 0.0558
4512 Cytochrome P450 3A4 CYP3A4 0.0515
6209 30S ribosomal protein S19 rpsS 0.0511
6712 30S ribosomal protein S19 rpsS 0.0511
6726 30S ribosomal protein S19 rpsS 0.0511
6207 30S ribosomal protein S14 rpsN 0.0511
1654 Interleukin-1 beta IL1B 0.0374
494 Caspase-1 CASP1 0.0297
183 Vascular endothelial growth factor A VEGFA 0.0284
1507 Cytochrome c CYCS 0.0272
308 30S ribosomal protein S12 rpsL 0.0248
6704 30S ribosomal protein S12 rpsL 0.0248
65 Matrix metalloproteinase-9 Not Available 0.0235
2077 Caspase-3 CASP3 0.0235
275 Arachidonate 5-lipoxygenase ALOX5 0.0227
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