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

Details

Stereochemistry ABSOLUTE
Molecular Formula C25H48N6O10
Molecular Weight 592.6838
Optical Activity UNSPECIFIED
Defined Stereocenters 12 / 12
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PLAZOMICIN

SMILES

C[C@@]1(CO[C@@]([H])([C@@]([H])([C@@]1([H])NC)O)O[C@@]2([H])[C@@]([H])(C[C@@]([H])([C@]([H])([C@]2([H])O)O[C@]3([H])[C@@]([H])(CC=C(CNCCO)O3)N)N)N=C([C@]([H])(CCN)O)O)O

InChI

InChIKey=IYDYFVUFSPQPPV-PEXOCOHZSA-N
InChI=1S/C25H48N6O10/c1-25(37)11-38-24(18(35)21(25)29-2)41-20-15(31-22(36)16(33)5-6-26)9-14(28)19(17(20)34)40-23-13(27)4-3-12(39-23)10-30-7-8-32/h3,13-21,23-24,29-30,32-35,37H,4-11,26-28H2,1-2H3,(H,31,36)/t13-,14+,15-,16+,17+,18-,19-,20+,21-,23-,24-,25+/m1/s1

HIDE SMILES / InChI

Molecular Formula C25H48N6O10
Molecular Weight 592.6838
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 12 / 12
E/Z Centers 0
Optical Activity UNSPECIFIED

Plazomicin is a novel aminoglycoside antibiotic that binds to the bacterial 30S ribosomal subunit, thus inhibiting protein synthesis in a concentration-dependent manner. Plazomicin displays a broad spectrum of activity against aerobic gram-negative bacteria including extended-spectrum β-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and organisms with aminoglycoside-modifying enzymes. Plazomicin resistance in Enterobacteriaceae is via modification of the ribosomal binding site due to expression of 16S rRNA methyltransferases. ZEMDRI (plazomicin) injection for intravenous use is indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
ZEMDRI

Approved Use

ZEMDRI is an aminoglycoside antibacterial indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis.

Launch Date

1529798400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
73.7 μg/mL
15 mg/kg single, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PLAZOMICIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
257 μg × h/mL
15 mg/kg single, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PLAZOMICIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.5 h
15 mg/kg single, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PLAZOMICIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
80%
15 mg/kg single, intravenous
dose: 15 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PLAZOMICIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
15 mg/kg 1 times / day multiple, intravenous
MTD
healthy, 18 to 65 years
Other AEs: Hypotension...
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Other AEs: Abdominal pain, Nausea...
Other AEs:
Abdominal pain (1.7%)
Nausea (10.5%)
Dizziness (8.8%)
Headache (7%)
Hypoesthesia (17.5%)
Flushing (1.7%)
Sources:
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Disc. AE: Vertigo, Dizziness...
AEs leading to
discontinuation/dose reduction:
Vertigo (1.3%)
Dizziness (2.7%)
Azotaemia (1.4%)
Hypotension (1.4%)
Type 2 diabetes mellitus (1.4%)
Sources:
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 39.5 years
Other AEs: Ototoxicity, Tinnitus...
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 59.4 years
Disc. AE: Blood creatinine increased...
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Disc. AE: Acute kidney injury, Chronic kidney disease...
AEs leading to
discontinuation/dose reduction:
Acute kidney injury (0.7%)
Chronic kidney disease (0.3%)
Metastatic neoplasm (0.3%)
Metastatic uterine cancer (0.3%)
Renal failure (0.3%)
Renal impairment (0.3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypotension grade 1-2
15 mg/kg 1 times / day multiple, intravenous
MTD
healthy, 18 to 65 years
Abdominal pain 1.7%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Flushing 1.7%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Nausea 10.5%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Hypoesthesia 17.5%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Headache 7%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Dizziness 8.8%
20 mg/kg 1 times / day single, intravenous
Highest studied dose
Dose: 20 mg/kg, 1 times / day
Route: intravenous
Route: single
Dose: 20 mg/kg, 1 times / day
Sources:
healthy, adult
Vertigo 1.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Azotaemia 1.4%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Hypotension 1.4%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Type 2 diabetes mellitus 1.4%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Dizziness 2.7%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 39.5 years
Tinnitus 1.3%
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 39.5 years
Ototoxicity 2.2%
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 39.5 years
Blood creatinine increased 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
unhealthy, mean age 59.4 years
Chronic kidney disease 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Metastatic neoplasm 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Metastatic uterine cancer 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Renal failure 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Renal impairment 0.3%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
Acute kidney injury 0.7%
Disc. AE
15 mg/kg 1 times / day multiple, intravenous
Recommended
Dose: 15 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 15 mg/kg, 1 times / day
Sources:
unhealthy, mean age 59.4 years
Health Status: unhealthy
Age Group: mean age 59.4 years
Sex: M+F
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no [IC50 6111 uM]
no [IC50 8712 uM]
no [IC50 8951 uM]
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes [IC50 1552 uM]
no (co-administration study)
Comment: IC50 value given as 1300 mcg/mL; mw of drug: 837.89; not an inhibitor in vivo when administered with metformin
Page: 16134
yes [IC50 403 uM]
no (co-administration study)
Comment: IC50 value given as 338 mcg/mL; mw of drug: 837.89; not an inhibitor in vivo when administered with metformin
Page: 16,96
yes
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Activity of a novel aminoglycoside, ACHN-490, against clinical isolates of Escherichia coli and Klebsiella pneumoniae from New York City.
2010 Oct
Plazomicin: A Novel Aminoglycoside for the Treatment of Resistant Gram-Negative Bacterial Infections.
2019 Feb
Plazomicin: A Next-Generation Aminoglycoside.
2019 Jan
Patents

Sample Use Guides

Administer ZEMDRI 15 mg/kg every 24 hours by intravenous (IV) infusion over 30 minutes to patients 18 years of age or older with creatinine clearance greater than or equal to 90 mL/min.
Route of Administration: Intravenous
MIC50/MIC90 values for plazomicin were the lowest of all the drugs tested: 0.5/0.5 mg/L for 96 KPC-producing Klebsiella pneumoniae isolates and 0.5/1 mg/L for all 110 carbapenemase-producing isolates.
Substance Class Chemical
Created
by admin
on Sat Jun 26 10:44:22 UTC 2021
Edited
by admin
on Sat Jun 26 10:44:22 UTC 2021
Record UNII
LYO9XZ250J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PLAZOMICIN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
(2S)-4-AMINO-N-((1R,2S,3S,4R,5S)-5-AMINO-4-(((2S,3R)-3-AMINO-6-(((2-HYDROXYETHYL)AMINO)METHYL)-3,4-DIHYDRO-2H-PYRAN-2-YL)OXY)-2-((3-DEOXY-4-C-METHYL-3-(METHYLAMINO)-.BETA.-L-ARABINOPYRANOSYL)OXY)-3-HYDROXYCYCLOHEXYL)-2-HYDROXYBUTANAMIDE
Common Name English
PLAZOMICIN [WHO-DD]
Common Name English
PLAZOMICIN [MI]
Common Name English
PLAZOMICIN [INN]
Common Name English
ACHN-490
Code English
PLAZOMICIN [USAN]
Common Name English
Code System Code Type Description
FDA UNII
LYO9XZ250J
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
DRUG CENTRAL
5287
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
INN
9522
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
WIKIPEDIA
Plazomicin
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
RXCUI
2049549
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
CAS
1154757-24-0
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
MERCK INDEX
M12109
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
NCI_THESAURUS
C174680
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
ChEMBL
CHEMBL1650559
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
LACTMED
Plazomicin
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
PUBCHEM
42613186
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
DRUG BANK
DB12615
Created by admin on Sat Jun 26 10:44:22 UTC 2021 , Edited by admin on Sat Jun 26 10:44:22 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
TARGET ORGANISM->INHIBITOR
EXCRETED UNCHANGED
Following a single IV dose of 15 mg/kg radiolabeled plazomicin, approximately 97.5% of the dose was recovered in the urine as unchanged plazomicin.
URINE
TRANSPORTER -> INHIBITOR
TARGET ORGANISM->INHIBITOR
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC