Identification

Name
Mezlocillin
Accession Number
DB00948  (APRD01113)
Type
Small Molecule
Groups
Approved, Investigational
Description

Semisynthetic ampicillin-derived acylureido penicillin. It has been proposed for infections with certain anaerobes and may be useful in inner ear, bile, and CNS infections. [PubChem]

Structure
Thumb
Synonyms
  • (2S,5R,6R)-3,3-Dimethyl-6-{[(2R)-2-({[3-(methylsulfonyl)-2-oxoimidazolidin-1-yl]carbonyl}amino)-2-phenylacetyl]amino}-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
  • 6beta-{(2R)-2-[3-(methanesulfonyl)-2-oxoimidazolidine-1-carboxamido]-2-phenylacetamido}penicillanic acid
  • Mezlocilina
  • Mezlocillin
  • Mezlocilline
  • Mezlocillinum
External IDs
BAY-F-1353
Product Ingredients
IngredientUNIICASInChI Key
Mezlocillin sodiumRX227TP94U42057-22-7GTGQRSIMEUWHPA-ZBJAFUORSA-M
Mezlocillin sodium monohydrate3CWW8B590480495-46-1CZXDIDROKIDGNE-SYNJJEHYSA-M
International/Other Brands
Mezlin
Categories
UNII
OH2O403D1G
CAS number
51481-65-3
Weight
Average: 539.582
Monoisotopic: 539.114454181
Chemical Formula
C21H25N5O8S2
InChI Key
YPBATNHYBCGSSN-VWPFQQQWSA-N
InChI
InChI=1S/C21H25N5O8S2/c1-21(2)14(18(29)30)26-16(28)13(17(26)35-21)22-15(27)12(11-7-5-4-6-8-11)23-19(31)24-9-10-25(20(24)32)36(3,33)34/h4-8,12-14,17H,9-10H2,1-3H3,(H,22,27)(H,23,31)(H,29,30)/t12-,13-,14+,17-/m1/s1
IUPAC Name
(2S,5R,6R)-6-[(2R)-2-[(3-methanesulfonyl-2-oxoimidazolidine-1-carbonyl)amino]-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
SMILES
[H][[email protected]]12SC(C)(C)[[email protected]@H](N1C(=O)[[email protected]]2NC(=O)[[email protected]](NC(=O)N1CCN(C1=O)S(C)(=O)=O)C1=CC=CC=C1)C(O)=O

Pharmacology

Indication

Used to treat serious gram–negative infections of the lungs, urinary tract, and skin.

Structured Indications
Not Available
Pharmacodynamics

Mezlocillin is a penicillin beta-lactam antibiotic used in the treatment of bacterial infections caused by susceptible, usually gram-positive, organisms. The name "penicillin" can either refer to several variants of penicillin available, or to the group of antibiotics derived from the penicillins. Mezlocillin has in vitro activity against gram-positive and gram-negative aerobic and anaerobic bacteria. The bactericidal activity of mezlocillin results from the inhibition of cell wall synthesis and is mediated through mezlocillin binding to penicillin binding proteins (PBPs). Mezlocillin is stable against hydrolysis by a variety of beta-lactamases, including penicillinases, and cephalosporinases and extended spectrum beta-lactamases. Mezlocillin can be used to treat susceptible strains of H. influenzae, Klebsiella species, Pseudomonas species, Proteus mirabilis, E. coli, Enterobacter species, Streptococcus faecelis, Peptococcus species, Peptostreptococcus species, Bacteriodes species (including B. fragilis), Morganella morganii, Serratia species, N. gonorrhoeae, P. vulgaris, and Providencia rettgeri. This drug is discontinued in the U.S.

Mechanism of action

By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, mezlocillin inhibits the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that mezlocillin interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 1A
inhibitor
Clostridium perfringens (strain 13 / Type A)
APenicillin-binding protein 3
inhibitor
Streptococcus pneumoniae
UPenicillin-binding protein 2
inhibitor
Escherichia coli (strain K12)
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

16-59%

Metabolism

Unlike many other penicillins, mezlocillin is either extensively metabolized or is subject to biliary excretion, as only about 50% of the dose was accounted for in normal urine.

Route of elimination
Not Available
Half life

1.3 to 4.4 hours

Clearance
Not Available
Toxicity

Symptoms of overdose include rash, fever, chills, and peeling skin.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolMezlocillin may increase the anticoagulant activities of Acenocoumarol.Approved
AclarubicinThe serum concentration of Aclarubicin can be decreased when it is combined with Mezlocillin.Investigational
AldoxorubicinThe serum concentration of Aldoxorubicin can be decreased when it is combined with Mezlocillin.Investigational
AmikacinThe serum concentration of Amikacin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
AmrubicinThe serum concentration of Amrubicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
AnnamycinThe serum concentration of Annamycin can be decreased when it is combined with Mezlocillin.Investigational
ApramycinThe serum concentration of Apramycin can be decreased when it is combined with Mezlocillin.Experimental, Vet Approved
ArbekacinThe serum concentration of Arbekacin can be decreased when it is combined with Mezlocillin.Approved, Investigational
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Mezlocillin.Investigational
BekanamycinThe serum concentration of Bekanamycin can be decreased when it is combined with Mezlocillin.Experimental
ChlortetracyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Chlortetracycline.Approved, Investigational, Vet Approved
ClorindioneMezlocillin may increase the anticoagulant activities of Clorindione.Experimental
DaunorubicinThe serum concentration of Daunorubicin can be decreased when it is combined with Mezlocillin.Approved
DemeclocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.Approved
DibekacinThe serum concentration of Dibekacin can be decreased when it is combined with Mezlocillin.Experimental
DicoumarolMezlocillin may increase the anticoagulant activities of Dicoumarol.Approved
DihydrostreptomycinThe serum concentration of Dihydrostreptomycin can be decreased when it is combined with Mezlocillin.Investigational, Vet Approved
DiphenadioneMezlocillin may increase the anticoagulant activities of Diphenadione.Experimental
DoxorubicinThe serum concentration of Doxorubicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
DoxycyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Doxycycline.Approved, Investigational, Vet Approved
EpirubicinThe serum concentration of Epirubicin can be decreased when it is combined with Mezlocillin.Approved
Ethyl biscoumacetateMezlocillin may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneMezlocillin may increase the anticoagulant activities of Fluindione.Investigational
FramycetinThe serum concentration of Framycetin can be decreased when it is combined with Mezlocillin.Approved
GeneticinThe serum concentration of Geneticin can be decreased when it is combined with Mezlocillin.Experimental
GentamicinThe serum concentration of Gentamicin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
GENTAMICIN C1AThe serum concentration of GENTAMICIN C1A can be decreased when it is combined with Mezlocillin.Experimental
GPX-150The serum concentration of GPX-150 can be decreased when it is combined with Mezlocillin.Investigational
Hygromycin BThe serum concentration of Hygromycin B can be decreased when it is combined with Mezlocillin.Vet Approved
IdarubicinThe serum concentration of Idarubicin can be decreased when it is combined with Mezlocillin.Approved
IsepamicinThe serum concentration of Isepamicin can be decreased when it is combined with Mezlocillin.Experimental
KanamycinThe serum concentration of Kanamycin can be decreased when it is combined with Mezlocillin.Approved, Investigational, Vet Approved
MedrogestoneThe serum concentration of Medrogestone can be decreased when it is combined with Mezlocillin.Approved
MethotrexateThe serum concentration of Methotrexate can be increased when it is combined with Mezlocillin.Approved
MetrizamideThe serum concentration of Metrizamide can be decreased when it is combined with Mezlocillin.Approved
MicronomicinThe serum concentration of Micronomicin can be decreased when it is combined with Mezlocillin.Experimental
MinocyclineThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Minocycline.Approved, Investigational
Mycophenolic acidThe serum concentration of the active metabolites of Mycophenolic acid can be reduced when Mycophenolic acid is used in combination with Mezlocillin resulting in a loss in efficacy.Approved
NeamineThe serum concentration of Neamine can be decreased when it is combined with Mezlocillin.Experimental
NeomycinThe serum concentration of Neomycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
NetilmicinThe serum concentration of Netilmicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
ParomomycinThe serum concentration of Paromomycin can be decreased when it is combined with Mezlocillin.Approved, Investigational
PhenindioneMezlocillin may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonMezlocillin may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Mezlocillin.Approved
PirarubicinThe serum concentration of Pirarubicin can be decreased when it is combined with Mezlocillin.Investigational
PlazomicinThe serum concentration of Plazomicin can be decreased when it is combined with Mezlocillin.Investigational
PlicamycinThe serum concentration of Plicamycin can be decreased when it is combined with Mezlocillin.Approved, Investigational, Withdrawn
ProbenecidThe serum concentration of Mezlocillin can be increased when it is combined with Probenecid.Approved
PuromycinThe serum concentration of Puromycin can be decreased when it is combined with Mezlocillin.Experimental
RibostamycinThe serum concentration of Ribostamycin can be decreased when it is combined with Mezlocillin.Approved, Investigational
SabarubicinThe serum concentration of Sabarubicin can be decreased when it is combined with Mezlocillin.Investigational
SisomicinThe serum concentration of Sisomicin can be decreased when it is combined with Mezlocillin.Investigational
SP1049CThe serum concentration of SP1049C can be decreased when it is combined with Mezlocillin.Investigational
SpectinomycinThe serum concentration of Spectinomycin can be decreased when it is combined with Mezlocillin.Approved, Investigational, Vet Approved
StreptomycinThe serum concentration of Streptomycin can be decreased when it is combined with Mezlocillin.Approved, Vet Approved
StreptozocinThe serum concentration of Streptozocin can be decreased when it is combined with Mezlocillin.Approved
TioclomarolMezlocillin may increase the anticoagulant activities of Tioclomarol.Experimental
TobramycinThe serum concentration of Tobramycin can be decreased when it is combined with Mezlocillin.Approved, Investigational
ValrubicinThe serum concentration of Valrubicin can be decreased when it is combined with Mezlocillin.Approved
WarfarinMezlocillin may increase the anticoagulant activities of Warfarin.Approved
Zoptarelin doxorubicinThe serum concentration of Zoptarelin doxorubicin can be decreased when it is combined with Mezlocillin.Investigational
ZorubicinThe serum concentration of Zorubicin can be decreased when it is combined with Mezlocillin.Experimental
Food Interactions
Not Available

References

General References
  1. Kristof RA, Clusmann H, Koehler W, Fink KB, Schramm J: Treatment of accidental high dose intraventricular mezlocillin application by cerebrospinal fluid exchange. J Neurol Neurosurg Psychiatry. 1998 Mar;64(3):379-81. [PubMed:9527154]
  2. McCormick PA, Greenslade L, Kibbler CC, Chin JK, Burroughs AK, McIntyre N: A prospective randomized trial of ceftazidime versus netilmicin plus mezlocillin in the empirical therapy of presumed sepsis in cirrhotic patients. Hepatology. 1997 Apr;25(4):833-6. [PubMed:9096584]
  3. Rohde B, Werner U, Hickstein H, Ehmcke H, Drewelow B: Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure. Eur J Clin Pharmacol. 1997;53(2):111-5. [PubMed:9403281]
External Links
Human Metabolome Database
HMDB15083
KEGG Drug
D05021
KEGG Compound
C07221
PubChem Compound
656511
PubChem Substance
46506692
ChemSpider
570894
ChEBI
6919
ChEMBL
CHEMBL1731
Therapeutic Targets Database
DAP001180
PharmGKB
PA164750540
Wikipedia
Mezlocillin
ATC Codes
J01CR50 — Combinations of penicillinsJ01CA10 — Mezlocillin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Bayer pharmaceuticals corp
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP0Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.471 mg/mLALOGPS
logP0.21ALOGPS
logP-0.84ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)3.49ChemAxon
pKa (Strongest Basic)-5.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area173.5 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity124.88 m3·mol-1ChemAxon
Polarizability51.5 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.8903
Blood Brain Barrier-0.9802
Caco-2 permeable-0.6285
P-glycoprotein substrateSubstrate0.7696
P-glycoprotein inhibitor INon-inhibitor0.817
P-glycoprotein inhibitor IINon-inhibitor0.9892
Renal organic cation transporterNon-inhibitor0.8761
CYP450 2C9 substrateNon-substrate0.5979
CYP450 2D6 substrateNon-substrate0.7973
CYP450 3A4 substrateNon-substrate0.5132
CYP450 1A2 substrateNon-inhibitor0.8033
CYP450 2C9 inhibitorNon-inhibitor0.7397
CYP450 2D6 inhibitorNon-inhibitor0.8934
CYP450 2C19 inhibitorNon-inhibitor0.7272
CYP450 3A4 inhibitorNon-inhibitor0.7478
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9747
Ames testNon AMES toxic0.6484
CarcinogenicityNon-carcinogens0.8275
BiodegradationReady biodegradable0.8269
Rat acute toxicity2.5003 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9907
hERG inhibition (predictor II)Non-inhibitor0.7489
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Peptides
Alternative Parents
Penicillins / N-carbamoyl-alpha amino acids and derivatives / N-acyl-alpha amino acids and derivatives / Alpha amino acid amides / Phenylacetamides / Sulfonylureas / Imidazolidinones / Thiazolidines / Tertiary carboxylic acid amides / Sulfonyls
show 13 more
Substituents
Alpha peptide / Penicillin / N-acyl-alpha amino acid or derivatives / N-carbamoyl-alpha-amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / Phenylacetamide / Penam / Sulfonylurea
show 33 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
penicillin (CHEBI:6919)

Targets

Kind
Protein
Organism
Clostridium perfringens (strain 13 / Type A)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transferase activity, transferring glycosyl groups
Specific Function
Cell wall formation. Synthesis of cross-linked peptidoglycan from the lipid intermediates. The enzyme has a penicillin-insensitive transglycosylase N-terminal domain (formation of linear glycan str...
Gene Name
pbpA
Uniprot ID
Q8XJ01
Uniprot Name
Penicillin-binding protein 1A
Molecular Weight
75176.35 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]
Kind
Protein
Organism
Streptococcus pneumoniae
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Not Available
Gene Name
pbp3
Uniprot ID
Q75Y35
Uniprot Name
Penicillin-binding protein 3
Molecular Weight
45209.84 Da
References
  1. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]
  2. Drugeon HB, Caillon J, Moinard D, Juvin ME, Pirault JL: [Bactericidal effect of piperacillin alone and combined]. Presse Med. 1986 Dec 20;15(46):2297-302. [PubMed:2949271]
  3. McCloskey RV, LeFrock JL, Smith BR, Aronoff GR: Microbiology, pharmacology, and clinical use of mezlocillin sodium. Pharmacotherapy. 1982 Nov-Dec;2(6):300-12. [PubMed:6220263]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name
mrdA
Uniprot ID
P0AD65
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
70856.1 Da
References
  1. Lei Y, Li JT: [Affinity of penicillin-binding proteins of Escherichia coli K-12 for furbenicillin and other beta-lactam antibiotics]. Zhongguo Yao Li Xue Bao. 1989 Mar;10(2):177-80. [PubMed:2683579]

Drug created on June 13, 2005 07:24 / Updated on January 18, 2018 22:43