AMDINOCILLIN PIVOXIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H33N3O5S
Molecular Weight	439.569
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=NPGNOVNWUSPMDP-UMEUOAKRSA-N

InChI=1S/C21H33N3O5S/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/b22-12-/t14-,15+,17-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01163
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Penicillin-binding protein 1A 45 Target ID: Q8DR59 Gene ID: 934791.0 Gene Symbol: pbpA Target Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845878	Inhibitor 8297	0.224 µM [IC50]
UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae 3 Target ID: UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845878	Inhibitor 8297	0.147 µM [IC50]
UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae 3 Target ID: UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/7447421	Inhibitor 8297	30.0 nM [IC50]
UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis 3 Target ID: UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120983	Inhibitor 8297	0.6 nM [IC50]
UniProtKB - L0BBN1, pbp3, Haemophilus influenzae 3 Target ID: UniProtKB - L0BBN1, pbp3, Haemophilus influenzae Sources: https://www.ncbi.nlm.nih.gov/pubmed/6972731	Inhibitor 8297	3.7 nM [IC50]
Penicillin-binding protein 2 24 Target ID: P0AD65 Gene ID: 945240.0 Gene Symbol: mrdA Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25733506	Inhibitor 8297	0.06 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.mims.com/india/drug/info/mecillinam?type=full&mtype=generic	Curative		Approved 8429	Mecillinam Approved Use Urinary tract infections Launch Date 1984

C_max

Value	Dose	Analyte	Population
87.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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

Value	Dose	Analyte	Population
112.97 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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

T_1/2

Value	Dose	Analyte	Population
0.886 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/	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

Dose	Population	Adverse events
500 mg single, intravenous Highest studied dose Dose: 500 mg Route: intravenous Route: single Dose: 500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/6311007 Page: p.83	healthy, 25 - 43 n = 12 Health Status: healthy Age Group: 25 - 43 Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6311007 Page: p.83	Sources: https://pubmed.ncbi.nlm.nih.gov/6311007 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 Page: p.110

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 Page: p.110

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-3276	http://www.3bsc.com/index/pro_info.php?id=76217
AHH Chemical co.,ltd	MT-53466	http://www.ahhchemical.com/product/MT-53466.html
Aaron Chemicals	AR00JL85	http://www.aaronchem.com/prod/32887-01-7
Ambeed	A678129	https://www.ambeed.com/products/32887-01-7.html
Aurora Fine Chemicals LLC	A17.900.971	http://online.aurorafinechemicals.com/info?ID=A17.900.971
BLD Pharm	BD137305	http://www.bldpharm.com/products/32887-01-7.html
CSNpharm	CSN11365	https://www.csnpharm.com/products/mecillinam.html
Chem Scene	CS-0017618	http://www.chemscene.com/32887-01-7.html
Chemspace	CSSB00016995348	https://chem-space.com/CSSB00016995348
Glentham Life Sciences	GA6807	http://www.glentham.com/products/product/GA6807/
Lab Network	LN01267525	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01267525
MedChem Express	HY-A0269	https://www.medchemexpress.com/mecillinam.html
Selleck Chemicals	S6584	http://www.selleckchem.com/products/amdinocillin.html
Sigma-Aldrich	33447_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/33447?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
abcr GmbH	AB479645	http://www.abcr.com/shop/en/AB479645
eNovation Chemicals	D673770	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673770

PubMed

Title	Date	PubMed
Microbiological evaluation of a commercial transport system for urine samples.	2002	12387577
Validation of FLEXICULT SSI-Urinary Kit for use in the primary health care setting.	2002	12160170
Mecillinam susceptibility as an indicator of beta-lactamase production in Staphylococcus aureus.	2002 Feb	11952728
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.	2002 Jun 1	12001235
Susceptibility of Danish Escherichia coli strains isolated from urinary tract infections and bacteraemia, and distribution of sul genes conferring sulphonamide resistance.	2002 Oct	12356795
Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.	2003 Dec	14613955
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	12519203
An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project.	2003 Jan	12493789
Identification of the CysB-regulated gene, hslJ, related to the Escherichia coli novobiocin resistance phenotype.	2003 Jul 29	12892888
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	12757942
Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance.	2004 Aug	15310182
Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC VR1310.	2004 Jun	15166212
Uncomplicated urinary tract infections. Bacterial findings and efficacy of empirical antibacterial treatment.	2005 Jun	16036551
Activity of mecillinam against ESBL producers in vitro.	2006 Feb	16354745
High-level resistance to mecillinam produced by inactivation of soluble lytic transglycosylase in Salmonella enterica serovar Typhimurium.	2006 Mar	16499622
The essential peptidoglycan glycosyltransferase MurG forms a complex with proteins involved in lateral envelope growth as well as with proteins involved in cell division in Escherichia coli.	2007 Aug	17640276
Evolutionary diversification of plant shikimate kinase gene duplicates.	2008 Dec	19057671
In vitro interaction between mecillinam and piperacillin-tazobactam in the presence of azithromycin against members of the Enterobacteriaceae family and Pseudomonas aeruginosa.	2008 Jan	18437840
Transfer of antimicrobial resistance plasmids from Klebsiella pneumoniae to Escherichia coli in the mouse intestine.	2008 Nov	18703526
RodZ, a new player in bacterial cell morphogenesis.	2009 Feb 4	19194484
Actinomyces species: A danish survey on human infections and microbiological characteristics.	2009 Jul 23	19657460
Multi-resistant Escherichia coli and mycotic aneurysm: two case reports.	2009 Mar 10	19830106
The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections.	2009 Nov	19505803
Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study.	2009 Oct 24	19852849
Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis?	2010 Oct	21123159
Extended-spectrum β-lactamases in Gram Negative Bacteria.	2010 Sep	20927289

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

AMDINOCILLIN PIVOXIL

Official Name

English

4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 6-(((HEXAHYDRO-1H-AZEPIN-1-YL)METHYLENE)AMINO)-3,3-DIMETHYL-7-OXO-, (2,2-DIMETHYL-1-OXOPROPOXY)METHYL ESTER, (2S-(2.ALPHA.,5.ALPHA.,6.BETA.))-

Common Name

English

Pivmecillinam [WHO-DD]

Common Name

English

PIVMECILLINAM [MART.]

Common Name

English

AMDINOCILLIN PIVOXIL [USAN]

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)

Common Name

English

pivmecillinam [INN]

Common Name

English

AMDINOCILLIN PIVOXIL [MI]

Common Name

English

PIVMECILLINAM

Official Name

English

PIVMECILLINAM [JAN]

Common Name

English

RO-10-9071

Code

English

RO 10-9071

Code

English

Classification Tree Code System Code

WHO-ATC

J01CA08