Details of the Drug

General Information of Drug (ID: DM3VOGS)

Drug Name
Ceftizoxime
Synonyms
Ceftix; Ceftizoxima; Ceftizoximum; Eposerin; Ceftizoxime Monosodium Salt; FK749; FR 13749; Cefizox (TN); Ceftizoxima[INN-Spanish]; Ceftizoxime (INN); Ceftizoxime [INN:BAN]; Ceftizoximum [INN-Latin]; FK-749; FR-13479; FR-13749; SKF-88373; SK&F 88373-2; Syn-7-(2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetamido)-3-cephem-4-carboxylic acid; (6R,7R)-7-(2-(2-Amino-4-thiazolyl)-2Z-(methoxyimino)acetamido)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-2-carbonsaeure; (6R,7R)-7-(2-(2-Amino-4-thiazolyl)glyoxyamido)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-carbonsaeure-7-(Z)-(O-methyloxim); (6R,7R)-7-({(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(methyloxy)imino]acetyl}amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid; 7beta-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-2,3-didehydropenam-2-carboxylic acid
Indication
Disease Entry ICD 11 Status REF
Bacterial infection 1A00-1C4Z Approved [1]
Therapeutic Class
Antibiotics
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 383.4
Topological Polar Surface Area (xlogp) 0
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 10
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 2.1 mL/min/kg [3]
Elimination
93% 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 1.5 hours [3]
Metabolism
The drug is not metabolised [4]
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 260.8194 micromolar/kg/day [5]
Unbound Fraction
The unbound fraction of drug in plasma is 0.72% [3]
Vd
The volume of distribution (Vd) of drug is 15-28 L [6]
Chemical Identifiers
Formula
C13H13N5O5S2
IUPAC Name
(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Canonical SMILES
CO/N=C(/C1=CSC(=N1)N)\\C(=O)N[C@H]2[C@@H]3N(C2=O)C(=CCS3)C(=O)O
InChI
InChI=1S/C13H13N5O5S2/c1-23-17-7(5-4-25-13(14)15-5)9(19)16-8-10(20)18-6(12(21)22)2-3-24-11(8)18/h2,4,8,11H,3H2,1H3,(H2,14,15)(H,16,19)(H,21,22)/b17-7-/t8-,11-/m1/s1
InChIKey
NNULBSISHYWZJU-LLKWHZGFSA-N
Cross-matching ID
PubChem CID
6533629
ChEBI ID
CHEBI:553473
CAS Number
68401-81-0
DrugBank ID
DB01332
TTD ID
D0Y7BD
VARIDT ID
DR00320

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 [7]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 4 (ABCC4) DTCSGPB MRP4_HUMAN Substrate [8]
Organic anion transporter 1 (SLC22A6) DTQ23VB S22A6_HUMAN Substrate [9]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [10]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ceftizoxime (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Plazomicin DMKMBES Moderate Increased risk of nephrotoxicity by the combination of Ceftizoxime and Plazomicin. Urinary tract infection [GC08] [45]

References

1 Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
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 Richards DM, Heel RC: Ceftizoxime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs. 1985 Apr;29(4):281-329. doi: 10.2165/00003495-198529040-00001.
7 Role of penicillin-binding protein 2 (PBP2) in the antibiotic susceptibility and cell wall cross-linking of Staphylococcus aureus: evidence for the cooperative functioning of PBP2, PBP4, and PBP2A. JBacteriol. 2005 Mar;187(5):1815-24.
8 Oral availability of cefadroxil depends on ABCC3 and ABCC4. Drug Metab Dispos. 2012 Mar;40(3):515-21.
9 FDA Drug Development and Drug Interactions
10 Human organic anion transporter hOAT3 is a potent transporter of cephalosporin antibiotics, in comparison with hOAT1. Biochem Pharmacol. 2005 Oct 1;70(7):1104-13.
11 Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport. J Pharmacol Exp Ther. 2007 Jan;320(1):229-35.
12 Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system. Cancer Res. 2002 Jun 1;62(11):3144-50.
13 ATP-binding cassette C transporters in human pancreatic carcinoma cell lines. Upregulation in 5-fluorouracil-resistant cells. Pancreatology. 2009;9(1-2):136-44.
14 The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9.
15 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
16 Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Biochem J. 2003 Apr 15;371(Pt 2):361-7.
17 P-glycoprotein, but not multidrug resistance protein 4, plays a role in the systemic clearance of irinotecan and SN-38 in mice. Drug Metab Lett. 2010 Dec;4(4):195-201.
18 Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia. Blood. 2009 Aug 13;114(7):1383-6.
19 Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Biochem J. 2002 Feb 1;361(Pt 3):497-503.
20 The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion-correlation of in vivo and in vitro studies. Drug Metab Dispos. 2002 Jan;30(1):13-9.
21 Transport of aminopterin by human organic anion transporters hOAT1 and hOAT3: Comparison with methotrexate. Drug Metab Pharmacokinet. 2010;25(2):163-9.
22 Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8.
23 Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther. 2002 Mar;300(3):918-24.
24 Expression levels of renal organic anion transporters (OATs) and their correlation with anionic drug excretion in patients with renal diseases. Pharm Res. 2004 Jan;21(1):61-7.
25 Multiple human isoforms of drug transporters contribute to the hepatic and renal transport of olmesartan, a selective antagonist of the angiotensin II AT1-receptor. Drug Metab Dispos. 2007 Dec;35(12):2166-76.
26 Interaction of zalcitabine with human organic anion transporter 1. Pharmazie. 2006 May;61(5):491-2.
27 Apical expression or expression in a non polarized cell of hOAT1 inverses regulation by epidermal growth factor (EGF) as compared to basolateral hOAT1. Cell Physiol Biochem. 2004;14(3):177-86.
28 Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Drug Metab Pharmacokinet. 2004 Oct;19(5):369-74.
29 Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86.
30 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
31 Murine renal organic anion transporters mOAT1 and mOAT3 facilitate the transport of neuroactive tryptophan metabolites. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1075-84.
32 Organic anion transporter 3 is involved in the brain-to-blood efflux transport of thiopurine nucleobase analogs. J Neurochem. 2004 Aug;90(4):931-41.
33 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
34 The contribution of organic anion transporters OAT1 and OAT3 to the renal uptake of rosuvastatin. J Pharmacol Exp Ther. 2007 Sep;322(3):1221-7.
35 Aspirin and probenecid inhibit organic anion transporter 3-mediated renal uptake of cilostazol and probenecid induces metabolism of cilostazol in the rat. Drug Metab Dispos. 2014 Jun;42(6):996-1007.
36 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.
37 Bacteriological characteristics of Staphylococcus aureus isolates from humans and bulk milk. J Dairy Sci. 2008 Feb;91(2):564-9.
38 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
39 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.
40 Emerging drugs for bacterial urinary tract infections. Expert Opin Emerg Drugs. 2005 May;10(2):275-98.
41 Penicillin-binding protein sensitive to cephalexin in sporulation of Bacillus cereus. Microbiol Res. 1997 Sep;152(3):227-32.
42 Clofarabine: past, present, and future. Leuk Lymphoma. 2007 Oct;48(10):1922-30.
43 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.
44 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.
45 Engle JE, Drago J, Carlin B, Schoolwerth AC "Letter: Reversible acute renal failure after cephalothin." Ann Intern Med 83 (1975): 232-3. [PMID: 1147461]