Details of the Drug

General Information of Drug (ID: DMSUVM1)

• Drug Name: Cefditoren
• Synonyms: Cefditoren [USAN:INN]; Meiact (TN); Spectracef (TN); (+)-(6R,7R)-7-(2-(2-Amino-4-thiazolyl)glyoxylamido)-3-((Z)-2-(4-methyl-5-thiazolyl)vinyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7(sup 2)-(Z)-(O-methyloxime); (6R-(3(Z),6alpha,7beta(Z)))-7-((2-Amino-4-thiazolyl)(methoxyimino)acetyl)amino-3-(2-(4-methyl-5-thiazolyl)ethenyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-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): 2:
  Molecular Weight (mw); 506.6
  Topological Polar Surface Area (xlogp); 0.7
  Rotatable Bond Count (rotbonds); 7
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 12
• ADMET Property:
  Clearance: The renal clearance of drug is 4-5 L/h [2]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.6 +/-0.4 hours [3]
  Vd: The volume of distribution (Vd) of drug is 9.3 +/- 1.6 L [2]
• Chemical Identifiers:
  Formula: C19H18N6O5S3
  IUPAC Name: (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(Z)-2-(4-methyl-1,3-thiazol-5-yl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
  Canonical SMILES: CC1=C(SC=N1)/C=C\\C2=C(N3[C@@H]([C@@H](C3=O)NC(=O)/C(=N\\OC)/C4=CSC(=N4)N)SC2)C(=O)O
  InChI: InChI=1S/C19H18N6O5S3/c1-8-11(33-7-21-8)4-3-9-5-31-17-13(16(27)25(17)14(9)18(28)29)23-15(26)12(24-30-2)10-6-32-19(20)22-10/h3-4,6-7,13,17H,5H2,1-2H3,(H2,20,22)(H,23,26)(H,28,29)/b4-3-,24-12-/t13-,17-/m1/s1
  InChIKey: KMIPKYQIOVAHOP-YLGJWRNMSA-N
• Cross-matching ID:
  PubChem CID: 9870843
  ChEBI ID: CHEBI:59343
  CAS Number: 104145-95-1
  DrugBank ID: DB01066
  TTD ID: D0E3RW
  VARIDT ID: DR01394

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Bacterial Penicillin binding protein (Bact PBP)	TTJP4SM	NOUNIPROTAC	Binder	[4]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[5]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Cefditoren

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Rabeprazole	DMMZXIW	Moderate	Decreased absorption of Cefditoren due to altered gastric pH caused by Rabeprazole.	Bacterial infection [1A00-1C4Z]	[22]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Sodium bicarbonate	DMMU6BJ	Moderate	Decreased absorption of Cefditoren due to altered gastric pH caused by Sodium bicarbonate.	Acidosis [5C73]	[22]
SODIUM CITRATE	DMHPD2Y	Moderate	Decreased absorption of Cefditoren due to altered gastric pH caused by SODIUM CITRATE.	Discovery agent [N.A.]	[22]
Dexlansoprazole	DM1DBV5	Moderate	Decreased absorption of Cefditoren due to altered gastric pH caused by Dexlansoprazole.	Gastro-oesophageal reflux disease [DA22]	[22]

References

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• [2] An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
• [3] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [4] Crystal structure of cefditoren complexed with Streptococcus pneumoniae penicillin-binding protein 2X: structural basis for its high antimicrobial ... Antimicrob Agents Chemother. 2007 Nov;51(11):3902-7.
• [5] Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. Pharmacol Rev. 2011 Mar;63(1):157-81.
• [6] Preclinical Mouse Models To Study Human OATP1B1- and OATP1B3-Mediated Drug-Drug Interactions in Vivo. Mol Pharm. 2015 Dec 7;12(12):4259-69.
• [7] Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide. Clin Cancer Res. 2013 Mar 15;19(6):1458-66.
• [8] Identification of drugs and drug metabolites as substrates of multidrug resistance protein 2 (MRP2) using triple-transfected MDCK-OATP1B1-UGT1A1-MRP2 cells. Br J Pharmacol. 2012 Mar;165(6):1836-1847.
• [9] The effect of SLCO1B1*15 on the disposition of pravastatin and pitavastatin is substrate dependent: the contribution of transporting activity changes by SLCO1B1*15. Pharmacogenet Genomics. 2008 May;18(5):424-33.
• [10] Influence of SLCO1B1, 1B3, 2B1 and ABCC2 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients. Eur J Clin Pharmacol. 2007 Dec;63(12):1161-9.
• [11] Rifampicin alters atorvastatin plasma concentration on the basis of SLCO1B1 521T>C polymorphism. Clin Chim Acta. 2009 Jul;405(1-2):49-52.
• [12] FDA Drug Development and Drug Interactions
• [13] Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob Agents Chemother. 2002 May;46(5):1273-80.
• [14] Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] Activities of antibiotics against methicillin-resistant Staphylococcus aureus with particular reference to synergetic effect between ticarcillin and fosfomycin on penicillinase non-producing methicillin-resistant S. aureus. Jpn J Antibiot. 1993 Jun;46(6):421-7.
• [17] Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
• [18] Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
• [19] Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
• [20] Relationship between penicillin-binding protein patterns and beta-lactamases in clinical isolates of Bacteroides fragilis with different susceptibility to beta-lactam antibiotics. J Med Microbiol. 2004 Mar;53(Pt 3):213-21.
• [21] Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J Antimicrob Chemother. 1990 Apr;25(4):513-23.
• [22] Product Information. Spectracef (cefditoren). TAP Pharmaceuticals Inc, Deerfield, IL.