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

Molecular Formula	C21H33N3O5S
Molecular Weight	439.569
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	1
Optical Activity	UNSPECIFIED

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
Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death.	1983 Aug 29	6311012
[Antibiotic resistance of E coli isolated from healthy persons].	2001 Sep 3	11571862
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	12596863
Mecillinam susceptibility of Auckland urinary isolates.	2002 Feb 8	11942520
Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.	2003 Dec	14613955
A new method for normalized interpretation of antimicrobial resistance from disk test results for comparative purposes.	2003 Feb	12588332
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
Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC VR1310.	2004 Jun	15166212
Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health.	2005	15871165
Prevalence of Shigella species and their antimicrobial resistance patterns in Eastern Nepal.	2005 Dec	16599104
Susceptibility testing of urinary isolates of Escherichia coli to mecillinam using NCCLS methodology.	2005 Mar	15737512
Intracellular persistence of Escherichia coli in urinary bladders from mecillinam-treated mice.	2005 Mar	15681580
Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli.	2005 May	15853883
[Increasing antibiotic resistance in urinary tract infections].	2006 Apr 6	16619066
Activity of mecillinam against AmpC beta-lactamase-producing Escherichia coli.	2006 Jul	16698846
DNA and origin region segregation are not affected by the transition from rod to sphere after inhibition of Escherichia coli MreB by A22.	2007 Jul	17581120
Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin.	2007 Jun	17985817
Function of penicillin-binding protein 2 in viability and morphology of Pseudomonas aeruginosa.	2007 Mar	17289762
Mecillinam: a low-risk antimicrobial agent for induction of Clostridium difficile infection in an in vitro human gut model.	2009 Apr	19211576
RodZ, a new player in bacterial cell morphogenesis.	2009 Feb 4	19194484
Influence of RpoS, cAMP-receptor protein, and ppGpp on expression of the opgGH operon and osmoregulated periplasmic glucan content of Salmonella enterica serovar Typhimurium.	2009 Nov	19940937
Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study.	2009 Oct 24	19852849
Activity of mecillinam against Escherichia coli resistant to third-generation cephalosporins.	2010 Jan	19915068
Acute uncomplicated cystitis: from surveillance data to a rationale for empirical treatment.	2010 Jan	19906513
Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis?	2010 Oct	21123159

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).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:13:20 GMT 2023` Edited by `admin` on `Fri Dec 15 17:13:20 GMT 2023`
Record UNII	1WAM1OQ30B
Record Status	`Validated (UNII)`
Record Version

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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