Details of the Drug

General Information of Drug (ID: DMRD1QK)

• Drug Name: Netilmicin
• Synonyms: NTL; Netilmicina; Netilmicine; Netilmicinum; Netilyn; Netira; Nettacin; Vectacin; NETILMICIN SULFATE; Sch 20569; Netilmicin (INN); Netilmicin [INN:BAN]; Netilmicina [INN-Spanish]; Netilmicine [INN-French]; Netilmicinum [INN-Latin]; Netira (TN); Nettacin (TN); Sch-20569; O-(2,6-Diamino-2,3,4,6-tetradesoxy-alpha-glycero-4-hexenopyranosyl-(1-4)-O-(3-desoxy-4-C-methyl-3-methylamino-beta-L-arabinopyranosyl-(1-6)-2-desoxy-N1-ethyl-D-streptamin; (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol; (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-amino-3-[[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol; (2R,3S,4S,5S)-2-[(1S,2R,3S,4S,6R)-4-amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol; 1-N-Aethylsisomicin; 1-N-Ethylsisomicin; 2-[4-amino-3-[[3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol; 4-amino-3-{[3-amino-6-(aminomethyl)-3,4-dihydro-2h-pyran-2-yl]oxy}-6-(ethylamino)-2-hydroxycyclohexyl 3-deoxy-4-c-methyl-3-(methylamino)pentopyranoside

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 3:
  Molecular Weight (mw); 475.6
  Logarithm of the Partition Coefficient (xlogp); -4.2
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 8
  Hydrogen Bond Acceptor Count (hbondacc); 12
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [2]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.55 mL/min/kg [3]
  Elimination: 85% of drug is excreted from urine in the unchanged form [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 2.5 hours [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 12.616 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 1% [3]
  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 0.073 L/kg [3]
• Chemical Identifiers:
  Formula: C21H41N5O7
  IUPAC Name: (2R,3R,4R,5R)-2-[(1S,2S,3R,4S,6R)-4-amino-3-[[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy]-6-(ethylamino)-2-hydroxycyclohexyl]oxy-5-methyl-4-(methylamino)oxane-3,5-diol
  Canonical SMILES: CCN[C@@H]1C[C@@H]([C@H]([C@@H]([C@H]1O[C@@H]2[C@@H]([C@H]([C@@](CO2)(C)O)NC)O)O)O[C@@H]3[C@@H](CC=C(O3)CN)N)N
  InChI: InChI=1S/C21H41N5O7/c1-4-26-13-7-12(24)16(32-19-11(23)6-5-10(8-22)31-19)14(27)17(13)33-20-15(28)18(25-3)21(2,29)9-30-20/h5,11-20,25-29H,4,6-9,22-24H2,1-3H3/t11-,12+,13-,14+,15-,16-,17+,18-,19-,20-,21+/m1/s1
  InChIKey: CIDUJQMULVCIBT-MQDUPKMGSA-N
• Cross-matching ID:
  PubChem CID: 441306
  CAS Number: 56391-56-1
  DrugBank ID: DB00955
  TTD ID: D07JZF
  INTEDE ID: DR1139

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	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Substrate	[6]
Aminoglycoside O-phosphotransferase (aphA6)	DEWPAJD	KKA6_ACIBA	Substrate	[7]
Aminoglycoside N-acetyltransferase (aacC2)	DEJADS9	AAC6_ACIBA	Substrate	[7]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Netilmicin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cefotetan	DM07TX3	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefotetan.	Bacterial infection [1A00-1C4Z]	[8]
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Kanamycin.	Bacterial infection [1A00-1C4Z]	[9]
Cefprozil	DM7DSYP	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefprozil.	Bacterial infection [1A00-1C4Z]	[8]
Ceftriaxone	DMCEW64	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Ceftriaxone.	Bacterial infection [1A00-1C4Z]	[8]
Streptomycin	DME1LQN	Moderate	Increased risk of ototoxicity by the combination of Netilmicin and Streptomycin.	Bacterial infection [1A00-1C4Z]	[9]
Cefepime	DMHVWIK	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefepime.	Bacterial infection [1A00-1C4Z]	[8]
Cefpodoxime	DMJUNY5	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefpodoxime.	Bacterial infection [1A00-1C4Z]	[8]
Rabeprazole	DMMZXIW	Moderate	Increased risk of hypomagnesemia by the combination of Netilmicin and Rabeprazole.	Bacterial infection [1A00-1C4Z]	[10]
Cefazolin	DMPDYFR	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefazolin.	Bacterial infection [1A00-1C4Z]	[8]
Cefoxitin	DMY8NC4	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefoxitin.	Bacterial infection [1A00-1C4Z]	[8]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Netilmicin caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[9]
Cefuroxime	DMSIMD8	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Cefuroxime.	Acute bronchitis [CA42]	[8]
Framycetin	DMF8DNE	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Framycetin.	Alcoholic liver disease [DB94]	[9]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Netilmicin and Inotersen.	Amyloidosis [5D00]	[11]
Etidronic acid	DM1XHYJ	Moderate	Increased risk of hypocalcemia by the combination of Netilmicin and Etidronic acid.	Bone paget disease [FB85]	[12]
Ketoprofen	DMRKXPT	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Ketoprofen.	Chronic pain [MG30]	[13]
Atracurium	DM42HXN	Major	Additive neuromuscular blocking effects by the combination of Netilmicin and Atracurium.	Corneal disease [9A76-9A78]	[14]
Mivacurium	DM473VD	Major	Additive neuromuscular blocking effects by the combination of Netilmicin and Mivacurium.	Corneal disease [9A76-9A78]	[14]
Pancuronium	DMB0VY8	Major	Additive neuromuscular blocking effects by the combination of Netilmicin and Pancuronium.	Corneal disease [9A76-9A78]	[14]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Netilmicin due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[15]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[9]
Balsalazide	DM7I1T9	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Balsalazide.	Indeterminate colitis [DD72]	[16]
Exjade	DMHPRWG	Major	Increased risk of nephrotoxicity by the combination of Netilmicin and Exjade.	Mineral absorption/transport disorder [5C64]	[17]
Neostigmine	DM6T2J3	Moderate	Additive neuromuscular blocking effects by the combination of Netilmicin and Neostigmine.	Myasthenia gravis [8C6Y]	[14]
Carboplatin	DMG281S	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Carboplatin.	Ovarian cancer [2C73]	[18]
Ibuprofen	DM8VCBE	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Ibuprofen.	Pain [MG30-MG3Z]	[13]
Choline salicylate	DM8P137	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[19]
Everolimus	DM8X2EH	Major	Increased risk of nephrotoxicity by the combination of Netilmicin and Everolimus.	Renal cell carcinoma [2C90]	[20]
Temsirolimus	DMS104F	Major	Increased risk of nephrotoxicity by the combination of Netilmicin and Temsirolimus.	Renal cell carcinoma [2C90]	[20]
Salsalate	DM13P4C	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Salsalate.	Rheumatoid arthritis [FA20]	[13]
Oxaprozin	DM9UB0P	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Oxaprozin.	Rheumatoid arthritis [FA20]	[13]
Ifosfamide	DMCT3I8	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[9]
Doxacurium	DMKE7L9	Major	Additive neuromuscular blocking effects by the combination of Netilmicin and Doxacurium.	Tonus and reflex abnormality [MB47]	[21]
Vecuronium	DMP0UK2	Major	Additive neuromuscular blocking effects by the combination of Netilmicin and Vecuronium.	Tonus and reflex abnormality [MB47]	[14]
Olsalazine	DMZW9HA	Moderate	Increased risk of nephrotoxicity by the combination of Netilmicin and Olsalazine.	Ulcerative colitis [DD71]	[16]
Plazomicin	DMKMBES	Moderate	Increased risk of ototoxicity by the combination of Netilmicin and Plazomicin.	Urinary tract infection [GC08]	[11]

References

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• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] 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
• [5] Ribosomal resistance in the gentamicin producer organism Micromonospora purpurea. Antimicrob Agents Chemother. 1982 Aug;22(2):231-6.
• [6] Aminoglycoside resistance resulting from tight drug binding to an altered aminoglycoside acetyltransferase. Antimicrob Agents Chemother. 2003 May;47(5):1577-83.
• [7] Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii. Chin Med J (Engl). 2005 Jan 20;118(2):141-5.
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• [9] Cerner Multum, Inc. "Australian Product Information.".
• [10] 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).".
• [11] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [12] Chang JT, Green L, Beitz J "Renal failure with the use of zoledronic acid." N Engl J Med 349 (2003): 1676-9 discussion 1676-9. [PMID: 14573746]
• [13] 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]
• [14] 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]
• [15] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [16] 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]
• [17] Product Information. Exjade (deferasirox). Novartis Pharmaceuticals, East Hanover, NJ.
• [18] Product Information. Paraplatin (carboplatin). Bristol-Myers Squibb, Princeton, NJ.
• [19] Farag MM, Mikhail MR, Abdel-Meguid E, Abdel-Tawab S "Assessment of gentamicin-induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium." Clin Sci 91 (1996): 187-91. [PMID: 8795442]
• [20] Product Information. Prograf (tacrolimus). Fujisawa, Deerfield, IL.
• [21] Geha DG, Blitt CD, Moon BJ "Prolonged neuromuscular blockade with pancuronium in the presence of acute renal failure: a case report." Anesth Analg 55 (1976): 343-5. [PMID: 945014]