Details of the Drug

General Information of Drug (ID: DM42W1B)

• Drug Name: Cefmetazole
• Synonyms: CMZ; Cefmetazolo; Cefmetazolum; Cefmetazole Monosodium Salt; CS 1170; SKF 83088; U 72791; CS-1170; Cefmetazole [USAN:INN]; Cefmetazolo [INN-Spanish]; Cefmetazolum [INN-Latin]; U-72791A; Cefmetazole (USP/INN); (6R,7S)-7-(2-((Cyanomethyl)thio)acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; (6R,7S)-7-(2-((Cyanomethyl)thio)acetamido)-7-methoxy-3-(((1-methyl-1H-tetrazol-5-yl)thiomethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, sodium salt; (6R,7S)-7-({[(cyanomethyl)sulfanyl]acetyl}amino)-7-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7S)-7-({[(cyanomethyl)thio]acetyl}amino)-7-(methyloxy)-3-{[(1-methyl-1H-tetrazol-5-yl)thio]methyl}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7S)-7-[[2-(cyanomethylsulfanyl)acetyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 6beta-{[(cyanomethyl)sulfanyl]acetamido}-6alpha-methoxy-3-{[(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl}ceph-3-em-4-carboxylic acid

Indication

Disease Entry	ICD 11	Status	REF
Bacterial infection	1A00-1C4Z	Approved	[1]
Pneumonia	CA40	Approved	[2]
Staphylococcal pneumonia	N.A.	Approved	[2]
Urinary tract infection	GC08	Approved	[2]

• Therapeutic Class: Antibiotics
• Affected Organisms: Enteric bacteria and other eubacteria
• ATC Code:
  J01DC09: Cefmetazole
  J01DC: Second-generation cephalosporins
  J01D: OTHER BETA-LACTAM ANTIBACTERIALS
  J01: ANTIBACTERIALS FOR SYSTEMIC USE
  J: ANTIINFECTIVES FOR SYSTEMIC USE
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 471.5
  Logarithm of the Partition Coefficient (xlogp); -0.6
  Rotatable Bond Count (rotbonds); 9
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 12
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [3]
  Bioavailability: The bioavailability of drug is 100% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.5 mL/min/kg [4]
  Elimination: 80% 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 1.50 +/- 0.14 hours [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 212.0717 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.15% [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 0.13 L/kg [4]
  Water Solubility: The ability of drug to dissolve in water is measured as 0.0942 mg/mL [3]
• Chemical Identifiers:
  Formula: C15H17N7O5S3
  IUPAC Name: (6R,7S)-7-[[2-(cyanomethylsulfanyl)acetyl]amino]-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  Canonical SMILES: CN1C(=NN=N1)SCC2=C(N3[C@@H]([C@@](C3=O)(NC(=O)CSCC#N)OC)SC2)C(=O)O
  InChI: InChI=1S/C15H17N7O5S3/c1-21-14(18-19-20-21)30-6-8-5-29-13-15(27-2,17-9(23)7-28-4-3-16)12(26)22(13)10(8)11(24)25/h13H,4-7H2,1-2H3,(H,17,23)(H,24,25)/t13-,15+/m1/s1
  InChIKey: SNBUBQHDYVFSQF-HIFRSBDPSA-N
• Cross-matching ID:
  PubChem CID: 42008
  ChEBI ID: CHEMBL1201195
  CAS Number: 56796-20-4
  UNII: 3J962UJT8H
  DrugBank ID: DB00274
  TTD ID: D05UBX
  VARIDT ID: DR00539
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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein 3 (Bact mrcA)	TT85JMW	FTSI_ECOLI	Binder	[6]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[7]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[8]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cefmetazole

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Kanamycin.	Bacterial infection [1A00-1C4Z]	[9]
Amikacin	DM5PDRB	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Amikacin.	Bacterial infection [1A00-1C4Z]	[9]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Streptomycin.	Bacterial infection [1A00-1C4Z]	[9]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Gentamicin.	Bacterial infection [1A00-1C4Z]	[9]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Tobramycin.	Bacterial infection [1A00-1C4Z]	[9]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Framycetin	DMF8DNE	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Framycetin.	Alcoholic liver disease [DB94]	[9]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Cefmetazole due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[10]
Ethanol	DMDRQZU	Moderate	Decreased metabolism of Cefmetazole caused by Ethanol mediated inhibition of non-CYP450 enzyme.	Cystitis [GC00]	[11]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Ethacrynic acid.	Essential hypertension [BA00]	[12]
Furosemide	DMMQ8ZG	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Furosemide.	Heart failure [BD10-BD1Z]	[12]
Bumetanide	DMRV7H0	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Bumetanide.	Heart failure [BD10-BD1Z]	[12]
Probenecid	DMMFWOJ	Moderate	Decreased elimination of Cefmetazole caused by Probenecid mediated competitive inhibition of renal tubular secretion.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[13]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Cefmetazole due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[10]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Cefmetazole and Plazomicin.	Urinary tract infection [GC08]	[14]

References

• [1] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050637.
• [2] Cefmetazole FDA Label
• [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] Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9.
• [7] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [8] Screening of antibiotics that interact with organic anion-transporting polypeptides 1B1 and 1B3 using fluorescent probes. Biol Pharm Bull. 2011;34(3):389-95.
• [9] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [10] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [11] Brown KR, Guglielmo BJ, Pons VG, Jacobs RA "Theophylline elixir, moxalactam, and a disulfiram reaction." Ann Intern Med 97 (1982): 621-2. [PMID: 6214982]
• [12] Chrysos G, Gargalianos P, Lelekis M, Stefanou J, Kosmidis J "Pharmacokinetic interactions of ceftazidime and frusemide." J Chemother 7 Suppl (1995): 107-10. [PMID: 8904125]
• [13] Brown G, Zemcov SJ, Clarke AM "Effect of probenecid on cefazolin serum concentrations." J Antimicrob Chemother 31 (1993): 1009-11. [PMID: 8360120]
• [14] Engle JE, Drago J, Carlin B, Schoolwerth AC "Letter: Reversible acute renal failure after cephalothin." Ann Intern Med 83 (1975): 232-3. [PMID: 1147461]