Details of the Drug

General Information of Drug (ID: DMVYSLE)

• Drug Name: Cefalotin
• Synonyms: Cefalothin; Cefalotina; Cefalotine; Cefalotinum; Cemastin; Cephalothinum; Cephalotin; Coaxin; Cefalotina fabra; Cephalothin Monosodium Salt; Averon-1; Cefalotin (BAN); Cefalotina [INN-Spanish]; Cefalotina fabra (TN); Cefalotine [INN-French]; Cefalotinum [INN-Latin]; Keflin (TN); (6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-3-[(acetyloxy)methyl]-8-oxo-7-[(2-thienylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 3-(Acetoxymethyl)-8-oxo-7-(2-(2-thienyl)acetamido)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid; 3-(Hydroxymethyl)-8-oxo-7-(2-(2-thienyl)acetamido)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid acetate; 3-ACETOXYMETHYL-8-OXO-7-(2-THIOPHEN-2-YL-ACETYLAMINO)-5-THIA-1-AZA-BICYCLO[4.2.0]OCT-2-ENE-2-CARBOXYLIC ACID; 3-Acetoxymethyl-7-(2-thienylacetamido)-3-cephem-4-carboxylic acid; 5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 3-(hydroxymethyl)-8-oxo-7-(2-(2-thienyl)acetamido)-, acetate (ester); 6R-trans-3-((Acetyloxy)methyl)-8-oxo-7-((2-thienylacetyl)amino)-5-thia-1-azabicyclo(4.2.0)-oct-2-ene-2-carboxylic acid; 7-(2-(2-Thienyl)acetylamido)cephalosporanic acid; 7-(2-Thienylacetamido)cephalosporanic acid; 7-(Thiophene-2-acetamido)cephalosporanic acid; 7-(Thiophene-2-acetamido)cephalosporin; 7beta-(thiophen-2-ylacetamido)-3-acetoxymethyl-3,4-didehydrocepham-4-carboxylic acid

Indication

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

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 396.4
  Topological Polar Surface Area (xlogp); -0.4
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 8
• 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 1.8 mL/min/kg [3]
  Elimination: 52% 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 30 minutes [3]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 252.24261 micromolar/kg/day [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.22% [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 0.07 L/kg [3]
  Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [2]
• Chemical Identifiers:
  Formula: C16H16N2O6S2
  IUPAC Name: (6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  Canonical SMILES: CC(=O)OCC1=C(N2[C@@H]([C@@H](C2=O)NC(=O)CC3=CC=CS3)SC1)C(=O)O
  InChI: InChI=1S/C16H16N2O6S2/c1-8(19)24-6-9-7-26-15-12(14(21)18(15)13(9)16(22)23)17-11(20)5-10-3-2-4-25-10/h2-4,12,15H,5-7H2,1H3,(H,17,20)(H,22,23)/t12-,15-/m1/s1
  InChIKey: XIURVHNZVLADCM-IUODEOHRSA-N
• Cross-matching ID:
  PubChem CID: 6024
  ChEBI ID: CHEBI:124991
  CAS Number: 153-61-7
  DrugBank ID: DB00456
  TTD ID: D01PLN
  INTEDE ID: DR2178

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial DD-carboxypeptidase (Bact vanYB)	TTLP6GN	VANY_ENTFA	Inhibitor	[5]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Beta-lactamase (blaB)	DET9I1W	BLAC_BACUN	Substrate	[6]
Beta-lactamase (blaB)	DENJ2SQ	BLAB_BACFG	Substrate	[7]
AmpC beta-lactamase (ampC)	DERI7LO	A0A0H3KQ39_BURM1	Substrate	[8]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cefalotin

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Kanamycin.	Bacterial infection [1A00-1C4Z]	[19]
Amikacin	DM5PDRB	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Amikacin.	Bacterial infection [1A00-1C4Z]	[19]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Streptomycin.	Bacterial infection [1A00-1C4Z]	[19]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Gentamicin.	Bacterial infection [1A00-1C4Z]	[19]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Tobramycin.	Bacterial infection [1A00-1C4Z]	[19]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Framycetin	DMF8DNE	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Framycetin.	Alcoholic liver disease [DB94]	[19]
Mycophenolic acid	DMU65NK	Moderate	Altered absorption of Cefalotin due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[20]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Ethacrynic acid.	Essential hypertension [BA00]	[21]
Furosemide	DMMQ8ZG	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Furosemide.	Heart failure [BD10-BD1Z]	[21]
Bumetanide	DMRV7H0	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Bumetanide.	Heart failure [BD10-BD1Z]	[21]
Probenecid	DMMFWOJ	Moderate	Decreased elimination of Cefalotin caused by Probenecid mediated competitive inhibition of renal tubular secretion.	Inborn purine/pyrimidine/nucleotide metabolism error [5C55]	[22]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Cefalotin due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[20]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Cefalotin and Plazomicin.	Urinary tract infection [GC08]	[19]

References

• [1] Cefalotin - FDA approved drug information (drug label) from DailyMed.
• [2] BDDCS applied to over 900 drugs
• [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] Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry. 1995 Jul 25;34(29):9532-40.
• [6] Purification and characterization of a new beta-lactamase from Bacteroides uniformis. Antimicrob Agents Chemother. 1995 Jul;39(7):1458-61.
• [7] Antibacterial activity of cefoperazone against anaerobic bacteria (author's transl). Jpn J Antibiot. 1980 Nov;33(11):1171-82.
• [8] Characterization of the AmpC beta-Lactamase from Burkholderia multivorans. Antimicrob Agents Chemother. 2018 Sep 24;62(10). pii: e01140-18.
• [9] Prevalence of antimicrobial resistance genes in Bacteroides spp. and Prevotella spp. Dutch clinical isolates. Clin Microbiol Infect. 2019 Sep;25(9):1156.e9-1156.e13.
• [10] Antimicrobial drugs used in the management of anaerobic infections in children. Drugs. 1983 Dec;26(6):520-9.
• [11] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [12] A 1.2-A snapshot of the final step of bacterial cell wall biosynthesis. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1427-31.
• [13] Extended-spectrum cephalosporinases: structure, detection and epidemiology. Future Microbiol. 2007 Jun;2:297-307.
• [14] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [15] Synthesis and evaluation of 3-(dihydroxyboryl)benzoic acids as D,D-carboxypeptidase R39 inhibitors. J Med Chem. 2009 Oct 8;52(19):6097-106.
• [16] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [17] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [18] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [19] Engle JE, Drago J, Carlin B, Schoolwerth AC "Letter: Reversible acute renal failure after cephalothin." Ann Intern Med 83 (1975): 232-3. [PMID: 1147461]
• [20] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [21] 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]
• [22] DiPiro JT, Welage LS, Levine BA, et al. Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery.?J Antimicrob Chemother. 1989;23 Suppl D:71-77. [PMID: 2722725]