Details of the Drug

General Information of Drug (ID: DM41GRA)

• Drug Name: Ceftazidime
• Synonyms: Ceftazidima; Ceftazidimum; Ceptaz; Fortaz; Ceftazidime Sodium In Plastic Container; Ceftazidime anhydrous; Ceftazidime pentahydrate; Fortaz In Plastic Container; SN 401; CEFTAZIDIME (ARGININE FORMULATION); Ceftazidima [INN-Spanish]; Ceftazidime (INN); Ceftazidime (TN); Ceftazidimum [INN-Latin]; Cefzim (TN); Ceptaz (TN); Fortaz (TN); Fortum (TN); (6R,7R)-7-({(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(1-carboxy-1-methylethoxy)imino]acetyl}amino)-8-oxo-3-(pyridinium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; (6R,7R)-7-[[(2E)-2-(2-amino-1,3-thiazol-4-yl)-2-(1-hydroxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(1-hydroxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; (6R,7R)-7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(1-hydroxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; (6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}-8-oxo-3-(pyridinium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; 7-[[2-(2-amino-1,3-thiazol-4-yl)-2-(1-hydroxy-2-methyl-1-oxopropan-2-yl)oxyiminoacetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate; 7beta-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetyl]amino}-3-(pyridinium-1-ylmethyl)-3,4-didehydrocepham-4-carboxylate

Indication

Disease Entry	ICD 11	Status	REF
Bacteremia	1A73	Approved	[1]
Bacterial infection	1A00-1C4Z	Approved	[2]
Endometritis	N.A.	Approved	[1]
Meningococcal meningitis	N.A.	Approved	[1]
Peritonitis	N.A.	Approved	[1]
Staphylococcal pneumonia	N.A.	Approved	[1]
Staphylococcus aureus infection	N.A.	Approved	[1]
Pelvic inflammatory disease	GA05	Investigative	[1]

• Therapeutic Class: Antibiotics
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 546.6
  Logarithm of the Partition Coefficient (xlogp); 0.4
  Rotatable Bond Count (rotbonds); 8
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 12
• ADMET Property:
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 42 mg/L [3]
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 3: high solubility and low permeability [4]
  Clearance: The renal clearance of drug is 72-141 mL/min [5]
  Elimination: Approximately 80% to 90% of an intramuscular or intravenous dose of ceftazidime is excreted unchanged by the kidneys over a 24-hour period [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.5 - 2.8 hours (in healthy subjects), and 14 - 30 (in patients with renal impairment) [3]
  Metabolism: The drug is not metabolised [5]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 156.81799 micromolar/kg/day [6]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.79% [7]
  Vd: The volume of distribution (Vd) of drug is 15-20 L [5]
  Water Solubility: The ability of drug to dissolve in water is measured as 5 mg/mL [4]
• Chemical Identifiers:
  Formula: C22H22N6O7S2
  IUPAC Name: (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  Canonical SMILES: CC(C)(C(=O)O)O/N=C(/C1=CSC(=N1)N)\\C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C[N+]4=CC=CC=C4)C(=O)[O-]
  InChI: InChI=1S/C22H22N6O7S2/c1-22(2,20(33)34)35-26-13(12-10-37-21(23)24-12)16(29)25-14-17(30)28-15(19(31)32)11(9-36-18(14)28)8-27-6-4-3-5-7-27/h3-7,10,14,18H,8-9H2,1-2H3,(H4-,23,24,25,29,31,32,33,34)/b26-13-/t14-,18-/m1/s1
  InChIKey: ORFOPKXBNMVMKC-DWVKKRMSSA-N
• Cross-matching ID:
  PubChem CID: 5481173
  ChEBI ID: CHEBI:3508
  CAS Number: 72558-82-8
  DrugBank ID: DB00438
  TTD ID: D0PH5Z
  VARIDT ID: DR00659
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[8]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-binding cassette sub-family C member 4 (ABCC4)	OTO27PAL	MRP4_HUMAN	Regulation of Drug Effects	[9]
Dihydrofolate reductase (DHFR)	OT3DVIGM	DYR_HUMAN	Gene/Protein Processing	[10]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Gene/Protein Processing	[11]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Ceftazidime

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Kanamycin	DM2DMPO	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Kanamycin.	Bacterial infection [1A00-1C4Z]	[12]
Ciprofloxacin XR	DM2NLS9	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Ciprofloxacin XR.	Bacterial infection [1A00-1C4Z]	[13]
Amikacin	DM5PDRB	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Amikacin.	Bacterial infection [1A00-1C4Z]	[12]
Sulfamethoxazole	DMB08GE	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Sulfamethoxazole.	Bacterial infection [1A00-1C4Z]	[13]
Streptomycin	DME1LQN	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Streptomycin.	Bacterial infection [1A00-1C4Z]	[12]
Gentamicin	DMKINJO	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Gentamicin.	Bacterial infection [1A00-1C4Z]	[12]
Netilmicin	DMRD1QK	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Netilmicin.	Bacterial infection [1A00-1C4Z]	[12]
Tobramycin	DMUI0CH	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Tobramycin.	Bacterial infection [1A00-1C4Z]	[12]

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

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Uracil mustard	DMHL7OB	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Uracil mustard.	Acute myeloid leukaemia [2A60]	[13]
Mycophenolic acid	DMRBMAU	Moderate	Altered absorption of Ceftazidime due to GI flora changes caused by Mycophenolic acid.	Crohn disease [DD70]	[14]
Ethacrynic acid	DM60QMR	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Ethacrynic acid.	Essential hypertension [BA00]	[15]
Pentamidine	DMHZJCG	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Pentamidine.	Fungal infection [1F29-1F2F]	[13]
Amphotericin B	DMTAJQE	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Amphotericin B.	Fungal infection [1F29-1F2F]	[13]
Furosemide	DMMQ8ZG	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Furosemide.	Heart failure [BD10-BD1Z]	[15]
Bumetanide	DMRV7H0	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Bumetanide.	Heart failure [BD10-BD1Z]	[15]
Zidovudine	DM4KI7O	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Zidovudine.	Human immunodeficiency virus disease [1C60-1C62]	[13]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[13]
Porfimer Sodium	DM7ZWNY	Moderate	Increased risk of photosensitivity reactions by the combination of Ceftazidime and Porfimer Sodium.	Lung cancer [2C25]	[16]
Melphalan	DMOLNHF	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Melphalan.	Multiple myeloma [2A83]	[13]
Cyclophosphamide	DM4O2Z7	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Cyclophosphamide.	Solid tumour/cancer [2A00-2F9Z]	[13]
Ifosfamide	DMCT3I8	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Ifosfamide.	Solid tumour/cancer [2A00-2F9Z]	[13]
Cisplatin	DMRHGI9	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Cisplatin.	Solid tumour/cancer [2A00-2F9Z]	[13]
Mycophenolate mofetil	DMPQAGE	Moderate	Altered absorption of Ceftazidime due to GI flora changes caused by Mycophenolate mofetil.	Transplant rejection [NE84]	[14]
Tacrolimus	DMZ7XNQ	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Tacrolimus.	Transplant rejection [NE84]	[13]
Plazomicin	DMKMBES	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Plazomicin.	Urinary tract infection [GC08]	[12]
Trimethoprim	DMM7CHK	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Trimethoprim.	Urinary tract infection [GC08]	[13]
Nalidixic acid	DMRM0JV	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Nalidixic acid.	Urinary tract infection [GC08]	[13]
Aciclovir	DMYLOVR	Moderate	Increased risk of nephrotoxicity by the combination of Ceftazidime and Aciclovir.	Virus infection [1A24-1D9Z]	[13]

References

• [1] Ceftazidime FDA Label
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] FDA Approved Drug Products: FORTAZ (ceftazidime) injection
• [4] BDDCS applied to over 900 drugs
• [5] Inoue K, Yuasa H: Molecular basis for pharmacokinetics and pharmacodynamics of methotrexate in rheumatoid arthritis therapy. Drug Metab Pharmacokinet. 2014;29(1):12-9. Epub 2013 Nov 26.
• [6] 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
• [7] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [8] New and emerging treatment of Staphylococcus aureus infections in the hospital setting. Clin Microbiol Infect. 2008 Apr;14 Suppl 3:32-41.
• [9] Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96.
• [10] Investigation of the effects of some drugs and phenolic compounds on human dihydrofolate reductase activity. J Biochem Mol Toxicol. 2015 Mar;29(3):135-9.
• [11] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
• [12] Agencia Espaola de Medicamentos y Productos Sanitarios Healthcare "Centro de informacion online de medicamentos de la AEMPS - CIMA.".
• [13] Cerner Multum, Inc. "Australian Product Information.".
• [14] Product Information. CellCept (mycophenolate mofetil). Roche Laboratories, Nutley, NJ.
• [15] 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]
• [16] Blakely KM, Drucker AM, Rosen CF "Drug-induced photosensitivity-an update: Culprit drugs, prevention and management." Drug Saf 42 (2019): 827-47. [PMID: 30888626]