Details of the Drug

General Information of Drug (ID: DM2DMPO)

• Drug Name: Kanamycin
• Synonyms: Aspidium; KAN; Kanamicina; Kanamycine; Kanamycinum; Kantrex; Klebcil; KANAMYCIN A; Kanamicina [Italian]; Kanamycin A tetracation; Kanamycin Base; Kanamycin monosulfate; Kanamycin sulfate; Kenamycin A; Liposomal Kanamycin; KM (the Antibiotic); Kanamycin [INN:BAN]; Kanamycin monosulfate (JP15); Kanamycinsulfate (JP15); Kanamycin sulfate (TN); Kanamycin sulfate (USP); Kanamycine [INN-French]; Kanamycinum [INN-Latin]; Kantrex (TN); Kantrex (1:1 sulfate); Klebcil (1:1 sulfate); O-3-amino-3-deoxy-alpha-D-glucopyranosyl-(1->6)-O-(6-amino-6-deoxy-alpha-D-glucopyranosyl-(1->4))-2-deoxy-D-streptamine; O-3-Amino-3-deoxy-.alpha.-D-glucopyranosyl-(1->6)-O-[6-amino-6-deoxy-.alpha.-D-glucopyranosyl-(1->4)]-2-deoxy-D-streptamine; (1S,2R,3R,4S,6R)-4,6-diamino-3-(6-amino-6-deoxy-alpha-D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-amino-3-deoxy-alpha-D-glucopyranoside; (1S,2R,3R,4S,6R)-4,6-diamino-3-[(6-amino-6-deoxy-alpha-D-glucopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-3-deoxy-alpha-D-glucopyranoside; (1S,2R,3R,4S,6R)-4,6-diazaniumyl-3-(6-azaniumyl-6-deoxy-alpha-D-glucopyranosyloxy)-2-hydroxycyclohexyl 3-azaniumyl-3-deoxy-alpha-D-glucopyranoside; (2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol; 4,6-Diamino-2-hydroxy-1,3-cyclohexane 3,6'diamino-3,6'-dideoxydi-alpha-D-glucoside; 4,6-diamino-2-hydroxy-1,3-cyclohexylene 3,6'-diamino-3,6'-dideoxydi-D-glucopyranoside

Indication

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[1]
Bacterial infection	1A00-1C4Z	Approved	[2]
Cholangitis	N.A.	Approved	[1]
Urinary tract infection	GC08	Approved	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 484.5
  Logarithm of the Partition Coefficient (xlogp); -6.9
  Rotatable Bond Count (rotbonds); 6
  Hydrogen Bond Donor Count (hbonddonor); 11
  Hydrogen Bond Acceptor Count (hbondacc); 15
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.4 mL/min/kg [4]
  Elimination: 90% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.1 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 30.95925 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.99% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.26 L/kg [4]
• Chemical Identifiers:
  Formula: C18H36N4O11
  IUPAC Name: (2R,3S,4S,5R,6R)-2-(aminomethyl)-6-[(1R,2R,3S,4R,6S)-4,6-diamino-3-[(2S,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol
  Canonical SMILES: C1[C@H]([C@@H]([C@H]([C@@H]([C@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CN)O)O)O)O)O[C@@H]3[C@@H]([C@H]([C@@H]([C@H](O3)CO)O)N)O)N
  InChI: InChI=1S/C18H36N4O11/c19-2-6-10(25)12(27)13(28)18(30-6)33-16-5(21)1-4(20)15(14(16)29)32-17-11(26)8(22)9(24)7(3-23)31-17/h4-18,23-29H,1-3,19-22H2/t4-,5+,6-,7-,8+,9-,10-,11-,12+,13-,14-,15+,16-,17-,18-/m1/s1
  InChIKey: SBUJHOSQTJFQJX-NOAMYHISSA-N
• Cross-matching ID:
  PubChem CID: 6032
  ChEBI ID: CHEBI:17630
  CAS Number: 59-01-8
  DrugBank ID: DB01172
  TTD ID: D0YV1Q
  VARIDT ID: DR01214
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Staphylococcus 30S ribosomal subunit (Stap-coc pbp2)	TTQ8KVI	F4NA87_STAAU	Binder	[6]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Aminoglycoside phosphotransferase (aph-Ib)	DE5WGIM	A0A075C7U3_CAMJU	Substrate	[7]
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Substrate	[8]
Kanamycin/gentamycin-resistance enzyme (aacA)	DECXWN8	J3S7E2_CAMCO	Substrate	[7]
Endoglucanase Y (EGY)	DE2M583	A0A256VAC0_LACRE	Substrate	[9]
Endoglucanase Y (EGY)	DE2AZTG	A0A256VAC0_LACRE	Substrate	[9]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
T-lymphocyte activation antigen CD86 (CD86)	OTJCSBPC	CD86_HUMAN	Gene/Protein Processing	[10]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Kanamycin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cefotetan	DM07TX3	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefotetan.	Bacterial infection [1A00-1C4Z]	[11]
Cefoperazone	DM53PV8	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefoperazone.	Bacterial infection [1A00-1C4Z]	[11]
Ceftriaxone	DMCEW64	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Ceftriaxone.	Bacterial infection [1A00-1C4Z]	[11]
Cefepime	DMHVWIK	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefepime.	Bacterial infection [1A00-1C4Z]	[11]
Cefpodoxime	DMJUNY5	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefpodoxime.	Bacterial infection [1A00-1C4Z]	[11]
Cefazolin	DMPDYFR	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefazolin.	Bacterial infection [1A00-1C4Z]	[11]
Cefonicid	DMTX2BH	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefonicid.	Bacterial infection [1A00-1C4Z]	[11]
Cefradine	DMUNSWV	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefradine.	Bacterial infection [1A00-1C4Z]	[12]
Cefoxitin	DMY8NC4	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefoxitin.	Bacterial infection [1A00-1C4Z]	[11]

Coadministration of a Drug Treating the Disease Different from Kanamycin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Kanamycin caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[13]
Cefamandole	DMNEXZF	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Cefamandole.	Anaerobic bacterial infection [1A00-1A09]	[11]
Iodipamide	DMXIQYS	Major	Increased risk of nephrotoxicity by the combination of Kanamycin and Iodipamide.	Cholelithiasis [DC11]	[14]
Atracurium	DM42HXN	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Atracurium.	Corneal disease [9A76-9A78]	[15]
Mivacurium	DM473VD	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Mivacurium.	Corneal disease [9A76-9A78]	[15]
Pancuronium	DMB0VY8	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Pancuronium.	Corneal disease [9A76-9A78]	[15]
Tubocurarine	DMBZIVP	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Tubocurarine.	Corneal disease [9A76-9A78]	[15]
Dexlansoprazole	DM1DBV5	Moderate	Increased risk of hypomagnesemia by the combination of Kanamycin and Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[16]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[13]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Kanamycin and Exjade.	Mineral absorption/transport disorder [5C64]	[17]
Neostigmine	DM6T2J3	Moderate	Additive neuromuscular blocking effects by the combination of Kanamycin and Neostigmine.	Myasthenia gravis [8C6Y]	[15]
Choline salicylate	DM8P137	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[18]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Kanamycin and Everolimus.	Renal cell carcinoma [2C90]	[19]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Kanamycin and Temsirolimus.	Renal cell carcinoma [2C90]	[19]
Salsalate	DM13P4C	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Salsalate.	Rheumatoid arthritis [FA20]	[18]
Ifosfamide	DMCT3I8	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[13]
Pipecuronium	DM5F84A	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Pipecuronium.	Tonus and reflex abnormality [MB47]	[15]
Vecuronium	DMP0UK2	Major	Additive neuromuscular blocking effects by the combination of Kanamycin and Vecuronium.	Tonus and reflex abnormality [MB47]	[15]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Olsalazine.	Ulcerative colitis [DD71]	[20]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Kanamycin and Plazomicin.	Urinary tract infection [GC08]	[13]

References

• [1] Kanamycin FDA Label
• [2] Novel agents in the management of Mycobacterium tuberculosis disease. Curr Med Chem. 2007;14(18):2000-8.
• [3] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] SsrA-mediated protein tagging in the presence of miscoding drugs and its physiological role in Escherichia coli. Genes Cells. 2002 Jul;7(7):629-38.
• [7] Cloning and expression of novel aminoglycoside phosphotransferase genes from Campylobacter and their role in the resistance to six aminoglycosides. Antimicrob Agents Chemother. 2017 Dec 21;62(1). pii: e01682-17.
• [8] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
• [9] Expression of Clostridium thermocellum endoglucanase gene in Lactobacillus gasseri and Lactobacillus johnsonii and characterization of the genetically modified probiotic lactobacilli. Curr Microbiol. 2000 Apr;40(4):257-63.
• [10] A plasmacytoid dendritic cell (CD123+/CD11c-) based assay system to predict contact allergenicity of chemicals. Toxicology. 2009 Oct 1;264(1-2):1-9. doi: 10.1016/j.tox.2009.07.021. Epub 2009 Aug 7.
• [11] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [12] Engle JE, Drago J, Carlin B, Schoolwerth AC "Letter: Reversible acute renal failure after cephalothin." Ann Intern Med 83 (1975): 232-3. [PMID: 1147461]
• [13] Cerner Multum, Inc. "Australian Product Information.".
• [14] Wong GT, Lee EY, Irwin MG. Contrast induced nephropathy in vascular surgery.?Br J Anaesth. 2016;117 Suppl 2:ii63-ii73. [PMID: 27566809]
• [15] Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF "Mutual potentiation of the neuromuscular effects of antibiotics and relaxants." Anesth Analg 58 (1979): 107-15. [PMID: 571233]
• [16] FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of proton pump inhibitor drugs (PPIs).".
• [17] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [18] Assael BM, Chiabrando C, Gagliardi L, Noseda A, Bamonte F, Salmona M "Prostaglandins and aminoglycoside nephrotoxicity." Toxicol Appl Pharmacol 78 (1985): 386-94. [PMID: 4049389]
• [19] Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
• [20] Novis BH, Korzets Z, Chen P, Bernheim J "Nephrotic syndrome after treatment with 5-aminosalicylic acid." Br Med J (Clin Res Ed) 296 (1988): 1442. [PMID: 3132281]