U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H33N3O5S.ClH
Molecular Weight 476.03
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of PIVMECILLINAM HYDROCHLORIDE

SMILES

Cl.[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2N=CN3CCCCCC3)C(=O)OCOC(=O)C(C)(C)C

InChI

InChIKey=UHPXMYLONAGUPC-YKBWBZKYSA-N
InChI=1S/C21H33N3O5S.ClH/c1-20(2,3)19(27)29-13-28-18(26)15-21(4,5)30-17-14(16(25)24(15)17)22-12-23-10-8-6-7-9-11-23;/h12,14-15,17H,6-11,13H2,1-5H3;1H/b22-12+;/t14-,15+,17-;/m1./s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://www.mims.com/india/drug/info/mecillinam?type=full&mtype=generic and https://www.ncbi.nlm.nih.gov/pubmed/3885172

Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms. Amdinocillin is not available in the United States.

CNS Activity

Curator's Comment: Poor penetration in humans

Originator

Curator's Comment: Mecillinam (Amdinocillin) developed by Leo Pharmaceuticals Balleherup, Denmark),

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: Q8DR59
Gene ID: 934791.0
Gene Symbol: pbpA
Target Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6)
0.224 µM [IC50]
Target ID: UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae
0.147 µM [IC50]
Target ID: UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae
30.0 nM [IC50]
Target ID: UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis
0.6 nM [IC50]
Target ID: UniProtKB - L0BBN1, pbp3, Haemophilus influenzae
3.7 nM [IC50]
Target ID: P0AD65
Gene ID: 945240.0
Gene Symbol: mrdA
Target Organism: Escherichia coli (strain K12)
0.06 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Mecillinam

Approved Use

Urinary tract infections

Launch Date

1984
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
87.3 μg/mL
15 mg/kg bw single, intravenous
dose: 15 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.3 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
3.2 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
3.6 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.1 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
49.5 μg/mL
10 mg/kg bw 6 times / day steady-state, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
26.2 μg/mL
10 mg/kg bw single, intramuscular
dose: 10 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
29.6 μg/mL
15 mg/kg bw single, intramuscular
dose: 15 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
49.4 μg/mL
10 mg/kg bw single, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
112.97 μg × h/mL
15 mg/kg bw single, intravenous
dose: 15 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
10 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
7.7 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.1 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
9.7 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
47.94 μg × h/mL
10 mg/kg bw single, intramuscular
dose: 10 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
72.15 μg × h/mL
15 mg/kg bw single, intramuscular
dose: 15 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
58.81 μg × h/mL
10 mg/kg bw single, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.886 h
15 mg/kg bw single, intravenous
dose: 15 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.9 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
1 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.9 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
52.39 min
10 mg/kg bw 6 times / day steady-state, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
54.38 min
10 mg/kg bw single, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.96 h
10 mg/kg bw single, intramuscular
dose: 10 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.859 h
15 mg/kg bw single, intramuscular
dose: 15 mg/kg bw
route of administration: Intramuscular
experiment type: SINGLE
co-administered:
AMDINOCILLIN serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
0.888 h
10 mg/kg bw single, intravenous
dose: 10 mg/kg bw
route of administration: Intravenous
experiment type: SINGLE
co-administered:
AMDINOCILLIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
500 mg single, intravenous
Highest studied dose
Dose: 500 mg
Route: intravenous
Route: single
Dose: 500 mg
Sources: Page: p.83
healthy, 25 - 43
n = 12
Health Status: healthy
Age Group: 25 - 43
Population Size: 12
Sources: Page: p.83
10 mg/kg 4 times / day multiple, intravenous
Studied dose
Dose: 10 mg/kg, 4 times / day
Route: intravenous
Route: multiple
Dose: 10 mg/kg, 4 times / day
Sources: Page: p.110
unhealthy, 25-94
n = 38
Health Status: unhealthy
Condition: gram-negative baciliary infections
Age Group: 25-94
Sex: M+F
Population Size: 38
Sources: Page: p.110
Other AEs: Diarrhea, Aspartate aminotransferase abnormal...
Other AEs:
Diarrhea (2.6%)
Aspartate aminotransferase abnormal (10.52%)
Alkaline phosphatase increased (7.9%)
Sources: Page: p.110
AEs

AEs

AESignificanceDosePopulation
Aspartate aminotransferase abnormal 10.52%
10 mg/kg 4 times / day multiple, intravenous
Studied dose
Dose: 10 mg/kg, 4 times / day
Route: intravenous
Route: multiple
Dose: 10 mg/kg, 4 times / day
Sources: Page: p.110
unhealthy, 25-94
n = 38
Health Status: unhealthy
Condition: gram-negative baciliary infections
Age Group: 25-94
Sex: M+F
Population Size: 38
Sources: Page: p.110
Diarrhea 2.6%
10 mg/kg 4 times / day multiple, intravenous
Studied dose
Dose: 10 mg/kg, 4 times / day
Route: intravenous
Route: multiple
Dose: 10 mg/kg, 4 times / day
Sources: Page: p.110
unhealthy, 25-94
n = 38
Health Status: unhealthy
Condition: gram-negative baciliary infections
Age Group: 25-94
Sex: M+F
Population Size: 38
Sources: Page: p.110
Alkaline phosphatase increased 7.9%
10 mg/kg 4 times / day multiple, intravenous
Studied dose
Dose: 10 mg/kg, 4 times / day
Route: intravenous
Route: multiple
Dose: 10 mg/kg, 4 times / day
Sources: Page: p.110
unhealthy, 25-94
n = 38
Health Status: unhealthy
Condition: gram-negative baciliary infections
Age Group: 25-94
Sex: M+F
Population Size: 38
Sources: Page: p.110
PubMed

PubMed

TitleDatePubMed
Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death.
1983 Aug 29
Efficacy of amdinocillin and lack of nephrotoxicity when combined with a second beta-lactam antibiotic for therapy of serious gram-negative bacillary infections.
1983 Aug 29
Microbiological evaluation of a commercial transport system for urine samples.
2002
Validation of FLEXICULT SSI-Urinary Kit for use in the primary health care setting.
2002
Novel S-benzylisothiourea compound that induces spherical cells in Escherichia coli probably by acting on a rod-shape-determining protein(s) other than penicillin-binding protein 2.
2002 Dec
Mecillinam susceptibility as an indicator of beta-lactamase production in Staphylococcus aureus.
2002 Feb
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.
2002 Jun 1
Susceptibility of Danish Escherichia coli strains isolated from urinary tract infections and bacteraemia, and distribution of sul genes conferring sulphonamide resistance.
2002 Oct
[Urinary tract pathogens in uncomplicated lower urinary tract infections in women in Norway].
2003 Aug 14
Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.
2003 Dec
A new method for normalized interpretation of antimicrobial resistance from disk test results for comparative purposes.
2003 Feb
Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole.
2003 Jan
An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project.
2003 Jan
Identification of the CysB-regulated gene, hslJ, related to the Escherichia coli novobiocin resistance phenotype.
2003 Jul 29
Null mutations in the essential gene yrfF (mucM) are not lethal in rcsB, yojN or rcsC strains of Salmonella enterica serovar Typhimurium.
2003 May 16
Pivmecillinam--therapy of choice for lower urinary tract infection.
2003 Oct
Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study.
2003 Oct
Localizing cell division in spherical Escherichia coli by nucleoid occlusion.
2003 Sep 26
Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance.
2004 Aug
Urinary concentrations and urine ex-vivo effect of mecillinam and sulphamethizole.
2004 Jan
Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC VR1310.
2004 Jun
Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health.
2005
Prevalence of Shigella species and their antimicrobial resistance patterns in Eastern Nepal.
2005 Dec
Uncomplicated urinary tract infections. Bacterial findings and efficacy of empirical antibacterial treatment.
2005 Jun
Susceptibility testing of urinary isolates of Escherichia coli to mecillinam using NCCLS methodology.
2005 Mar
Intracellular persistence of Escherichia coli in urinary bladders from mecillinam-treated mice.
2005 Mar
Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli.
2005 May
Isolation and characterization of provisional serovar Shigella boydii E16553 from diarrhoeal patients in Bangladesh.
2005 May
Partition of old murein in small patches over the entire wall of E. coli cells forced to grow as a coccoid.
2006 Apr
The emerging strains of Shigella dysenteriae type 2 in Bangladesh are clonal.
2006 Dec
Activity of mecillinam against ESBL producers in vitro.
2006 Feb
High-level resistance to mecillinam produced by inactivation of soluble lytic transglycosylase in Salmonella enterica serovar Typhimurium.
2006 Mar
The diversity of multi-drug resistance profiles in tetracycline-resistant Vibrio species isolated from coastal sediments and seawater.
2007 Feb
Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin.
2007 Jun
Evolutionary diversification of plant shikimate kinase gene duplicates.
2008 Dec
In vitro interaction between mecillinam and piperacillin-tazobactam in the presence of azithromycin against members of the Enterobacteriaceae family and Pseudomonas aeruginosa.
2008 Jan
Dissemination of multidrug-resistant bacteria into the Arctic.
2008 Jan
Transfer of antimicrobial resistance plasmids from Klebsiella pneumoniae to Escherichia coli in the mouse intestine.
2008 Nov
Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy.
2008 Nov
Endemic and epidemic lineages of Escherichia coli that cause urinary tract infections.
2008 Oct
Multi-resistant Escherichia coli and mycotic aneurysm: two case reports.
2009 Mar 10
Bend into shape.
2009 May 6
The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections.
2009 Nov
Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study.
2009 Oct 24
[Clinical aspects and epidemiology of uncomplicated cystitis in women. German results of the ARESC Study].
2010 Feb
Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use.
2010 Feb 16
Septal and lateral wall localization of PBP5, the major D,D-carboxypeptidase of Escherichia coli, requires substrate recognition and membrane attachment.
2010 Jul
Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis?
2010 Oct
Extended-spectrum β-lactamases in Gram Negative Bacteria.
2010 Sep
Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.
2010 Sep 30
Patents

Patents

Sample Use Guides

Parenteral Urinary tract infections Adult: 800 mg every 6-8 hr by IM, slow IV inj or IV infusion. Severe infections: Up to 60 mg/kg/day.
Route of Administration: Parenteral
Amdinocillin (Mecillinam) selectively inhibited PBP1, with a 50% inhibitory concentration for PBP1 binding (0.2 ug/ml) similar to the MIC (0.1 ug/ml) and minimum bactericidal concentration (0.25 ug/ml).
Name Type Language
PIVMECILLINAM HYDROCHLORIDE
EP   MART.   WHO-DD  
Common Name English
Pivmecillinam hydrochloride [WHO-DD]
Common Name English
PIVMECILLINAM HYDROCHLORIDE [MART.]
Common Name English
AMDINOCILLIN PIVOXIL HYDROCHLORIDE
MI  
Common Name English
PIVMECILLINAM HYDROCHLORIDE [JAN]
Common Name English
PIVMECILLINAM HYDROCHLORIDE [EP MONOGRAPH]
Common Name English
AMDINOCILLIN PIVOXIL HYDROCHLORIDE [MI]
Common Name English
HYDROXYMETHYL (2S,5R,6R)-6-(((HEXAHYDRO-1H-AZEPIN-1-YL)METHYLENE)AMINO)-3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLATE PIVALATE (ESTER) HYDROCHLORIDE
Common Name English
1H-AZEPIN-1-YL)METHYLENE)AMINO)-3,3-DIMETHYL-7-OXO-, HYDROXYMETHYL ESTER PIVALATE (ESTER), MONOHYDROCHLORIDE, (+)-
Common Name English
Code System Code Type Description
EVMPD
SUB03884MIG
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
RXCUI
102745
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY RxNorm
CHEBI
51213
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
CAS
32887-03-9
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
ChEMBL
CHEMBL1650818
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
MERCK INDEX
m1654
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY Merck Index
DRUG BANK
DBSALT001943
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
FDA UNII
48FX7N21H2
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
ECHA (EC/EINECS)
251-278-7
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
EPA CompTox
DTXSID1045453
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
SMS_ID
100000091362
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY
PUBCHEM
115162
Created by admin on Fri Dec 15 15:26:08 GMT 2023 , Edited by admin on Fri Dec 15 15:26:08 GMT 2023
PRIMARY