DT-Web

DB00684 - Tobramycin


Identification
Name Tobramycin
Accession Number DB00684 (APRD00582)
Type small molecule
Description An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the pseudomonas species. It is a 10% component of the antibiotic complex, nebramycin, produced by the same species. [PubChem]
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 467.5145
Groups approved
Monoisotopic Weight 467.259127807
Pharmacology
Indication For the treatment of pseudomonas aeruginosa lung infections. Also being investigated for use in the treatment of sinus infections.
Mechanism of action Tobramycin binds irreversibly to one of two aminoglycoside binding sites on the 30 S ribosomal subunit, inhibiting bacterial protein synthesis. Tobramycin may also destabilize bacterial memebrane by binding to 16 S 16 S r-RNA. An active transport mechanism for aminoglycoside uptake is necessary in the bacteria in order to attain a significant intracellular concentration of tobramycin.
Absorption The bioavailability of tobramycin may vary because of individual differences in nebulizer performance and airway pathology.
Protein binding Not Available
Biotransformation Not Available
Route of elimination Not Available
Toxicity LD50=441mg/kg (s.c. in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetazolamide Increased risk of nephrotoxicity
Amphotericin B Increased risk of nephrotoxicity
Atracurium The agent increases the effect of the muscle relaxant
Benazepril Increased risk of nephrotoxicity
Bumetanide Increased ototoxicity
Candesartan Increased risk of nephrotoxicity
Captopril Increased risk of nephrotoxicity
Cefamandole Increased risk of nephrotoxicity
Cefazolin Increased risk of nephrotoxicity
Cefonicid Increased risk of nephrotoxicity
Cefoperazone Increased risk of nephrotoxicity
Ceforanide Increased risk of nephrotoxicity
Cefotaxime Increased risk of nephrotoxicity
Cefotetan Increased risk of nephrotoxicity
Cefoxitin Increased risk of nephrotoxicity
Cefradine Increased risk of nephrotoxicity
Ceftazidime Increased risk of nephrotoxicity
Ceftizoxime Increased risk of nephrotoxicity
Ceftriaxone Increased risk of nephrotoxicity
Cefuroxime Increased risk of nephrotoxicity
Cephalothin Group Increased risk of nephrotoxicity
Cephapirin Increased risk of nephrotoxicity
Cisplatin Increased risk of nephrotoxicity
Colistimethate Increased risk of nephrotoxicity
Cyclosporine Increased risk of nephrotoxicity
Didanosine Increased risk of nephrotoxicity
Doxacurium chloride The agent increases the effect of the muscle relaxant
Enalapril Increased risk of nephrotoxicity
Ethacrynic acid Increased ototoxicity
Fosinopril Increased risk of nephrotoxicity
Furosemide Increased ototoxicity
Heparin Increased risk of nephrotoxicity
Irbesartan Increased risk of nephrotoxicity
Lamivudine Increased risk of nephrotoxicity
Lisinopril Increased risk of nephrotoxicity
Lithium Increased risk of nephrotoxicity
Losartan Increased risk of nephrotoxicity
Metocurine The agent increases the effect of the muscle relaxant
Mivacurium The agent increases the effect of the muscle relaxant
Olmesartan Increased risk of nephrotoxicity
Pancuronium The agent increases the effect of the muscle relaxant
Perindopril Increased risk of nephrotoxicity
Phenytoin Increased risk of nephrotoxicity
Pipecuronium The agent increases the effect of the muscle relaxant
Quinapril Increased risk of nephrotoxicity
Ramipril Increased risk of nephrotoxicity
Rocuronium The agent increases the effect of the muscle relaxant
Spironolactone Increased risk of nephrotoxicity
Succinylcholine The agent increases the effect of the muscle relaxant
Sulfamethoxazole Increased risk of nephrotoxicity
Tacrolimus Additive renal impairment may occur during concomitant therapy with aminoglycosides such as Tobramycin. Use caution during concomitant therapy.
Telmisartan Increased risk of nephrotoxicity
Thalidomide Thalidomide increases the renal toxicity of the aminoglycoside
Ticarcillin Ticarcillin may reduce the serum concentration of Tobramycin. Ticarcillin may inactivate Tobramycin in vitro and the two agents should not be administered simultaneously through the same IV line.
Topiramate Increased risk of nephrotoxicity
Torasemide Increased ototoxicity
Trimethoprim Increased risk of nephrotoxicity
Tubocurarine The agent increases the effect of the muscle relaxant
Valsartan Increased risk of nephrotoxicity
Vancomycin Increased risk of nephrotoxicity
Vecuronium The agent increases the effect of the muscle relaxant
Food Interactions Not Available

Targets


30S ribosomal protein S12
Name 30S ribosomal protein S12
Gene Name rpsL
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
  • Gill AE, Amyes SG: The contribution of a novel ribosomal S12 mutation to aminoglycoside resistance of Escherichia coli mutants. J Chemother. 2004 Aug;16(4):347-9. - Pubmed
  • Yang G, Trylska J, Tor Y, McCammon JA: Binding of aminoglycosidic antibiotics to the oligonucleotide A-site model and 30S ribosomal subunit: Poisson-Boltzmann model, thermal denaturation, and fluorescence studies. J Med Chem. 2006 Sep 7;49(18):5478-90. - Pubmed
DTHybrid score 1.2804
16S rRNA
Name 16S rRNA
Gene Name Not Available
Pharmacological action unknown
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
  • Doi Y, de Oliveira Garcia D, Adams J, Paterson DL: Coproduction of novel 16S rRNA methylase RmtD and metallo-beta-lactamase SPM-1 in a panresistant Pseudomonas aeruginosa isolate from Brazil. Antimicrob Agents Chemother. 2007 Mar;51(3):852-6. Epub 2006 Dec 11. - Pubmed
  • Bogaerts P, Galimand M, Bauraing C, Deplano A, Vanhoof R, De Mendonca R, Rodriguez-Villalobos H, Struelens M, Glupczynski Y: Emergence of ArmA and RmtB aminoglycoside resistance 16S rRNA methylases in Belgium. J Antimicrob Chemother. 2007 Mar;59(3):459-64. Epub 2007 Jan 15. - Pubmed
  • Chen SY, Lin TH: A molecular dynamics study on binding recognition between several 4,5 and 4,6-linked aminoglycosides with A-site RNA. J Mol Recognit. 2009 Dec 22. - Pubmed
DTHybrid score Not Available

Enzymes


Aminoglycoside 2'-N-acetyltransferase
Name Aminoglycoside 2'-N-acetyltransferase
Gene Name aac
Actions substrate
References
  • Vetting MW, Hegde SS, Javid-Majd F, Blanchard JS, Roderick SL: Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. Nat Struct Biol. 2002 Sep;9(9):653-8. - Pubmed
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
6704 30S ribosomal protein S12 rpsL 1.2804
4240 Protein disulfide-isomerase P4HB 0.1513
3390 Aminoglycoside 3'-phosphotransferase aphA 0.1389
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.1389
6028 Kanamycin nucleotidyltransferase knt 0.1388
4565 Aminoglycoside 6'-N-acetyltransferase aac(6')-Iy 0.1355
5682 Ribonuclease pancreatic RNASE1 0.1013
1162 C-X-C chemokine receptor type 4 CXCR4 0.0691
1244 Low-density lipoprotein receptor-related protein 2 LRP2 0.0525
1729 Solute carrier family 22 member 6 SLC22A6 0.044
6208 30S ribosomal protein S13 rpsM 0.0281
6706 30S ribosomal protein S13 rpsM 0.0281
6209 30S ribosomal protein S19 rpsS 0.0245
6712 30S ribosomal protein S19 rpsS 0.0245
6726 30S ribosomal protein S19 rpsS 0.0245
6207 30S ribosomal protein S14 rpsN 0.0245
140 30S ribosomal protein S9 rpsI 0.0185
6719 30S ribosomal protein S9 rpsI 0.0185
6725 30S ribosomal protein S9 rpsI 0.0185
4576 Aac(6')-Ii protein aac(6')-Ii 0.0098
4579 Serine acetyltransferase cysE 0.0098
6807 Serine acetyltransferase cysE 0.0098
4567 Putative acyl-CoA thioester hydrolase HI0827 HI_0827 0.0098
4564 YvbK protein yvbK 0.0098
4566 Acyl-CoA hydrolase BC_2038 0.0098
4572 Acyl-CoA hydrolase BH0798 0.0098
4037 Hypothetical protein GPX1 0.0098
4297 Hypothetical protein SP_1951 0.0098
4521 Hypothetical protein BC_2969 0.0098
4540 Hypothetical protein TM_1070 0.0098
4555 Hypothetical protein MT1739 0.0098
4569 Hypothetical protein mshD 0.0098
4578 Hypothetical protein PA3270 0.0098
4747 Hypothetical protein PA3967 0.0098
5177 Hypothetical protein TM_0096 0.0098
5194 Hypothetical protein PA1204 0.0098
5240 Hypothetical protein Rv2991 0.0098
5370 Hypothetical protein TM_1158 0.0098
5710 Hypothetical protein Tb927.5.1360 0.0098
4577 4'-phosphopantetheinyl transferase sfp sfp 0.0098
2528 Fatty acid metabolism regulator protein fadR 0.0098
6740 Fatty acid metabolism regulator protein fadR 0.0098
3489 Acetyl-coenzyme A synthetase acs 0.0085
3560 Gentamicin 3'-acetyltransferase aacC1 0.0085
2396 Formyl-coenzyme A transferase frc 0.0085
3457 Formyl-coenzyme A transferase frc 0.0085
4574 PROBABLE NAPHTHOATE SYNTHASE MENB menB 0.0085
3024 Crotonobetainyl-CoA:carnitine CoA-transferase caiB 0.0085
3317 Holo-[acyl-carrier-protein] synthase acpS 0.0084
4381 Holo-[acyl-carrier-protein] synthase acpS 0.0084
3125 Protease synthase and sporulation negative regulatory protein PAI 1 paiA 0.0084
4563 Acetyl transferase rimL 0.0084
3729 Citrate synthase gltA 0.0084
4575 Citrate synthase cit 0.0084
4580 Citrate synthase gltA 0.0084
2409 Acetyl-CoA acetyltransferase, cytosolic ACAT2 0.0084
2560 Galactoside O-acetyltransferase lacA 0.008
3697 Bifunctional protein glmU [Includes: UDP-N-acetylglucosamine pyrophosphorylase glmU 0.0078
3178 Formate acetyltransferase 1 pflB 0.0078
3199 Phosphopantetheine adenylyltransferase coaD 0.0078
3543 Phosphopantetheine adenylyltransferase coaD 0.0078
3567 Phosphopantetheine adenylyltransferase coaD 0.0078
5289 Phosphopantetheine adenylyltransferase coaD 0.0078
2377 Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex Not Available 0.0078
2285 Streptogramin A acetyltransferase vatD 0.0078
4573 Histone acetyltransferase PCAF KAT2B 0.0078
2248 Malate synthase G glcB 0.0077
3190 Malate synthase G glcB 0.0077
2371 Pantothenate kinase coaA 0.0077
4404 FcbC1 protein fcbC 0.0074
2376 2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferase dapD 0.007
551 Carnitine O-acetyltransferase CRAT 0.007
615 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 0.0064
3138 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 0.0064
4568 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 0.0064
6370 3-oxoacyl-[acyl-carrier-protein] synthase 3 fabH 0.0064
2596 Acetyl-CoA acetyltransferase phbA 0.0064
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0049
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0049
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