Details
Stereochemistry | ABSOLUTE |
Molecular Formula | 2C25H48N6O10.5H2O4S |
Molecular Weight | 1675.758 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 24 / 24 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.OS(O)(=O)=O.CN[C@@H]1[C@@H](O)[C@@H](O[C@H]2[C@@H](C[C@H](N)[C@@H](O[C@H]3OC(CNCCO)=CC[C@H]3N)[C@@H]2O)NC(=O)[C@@H](O)CCN)OC[C@]1(C)O.CN[C@@H]4[C@@H](O)[C@@H](O[C@H]5[C@@H](C[C@H](N)[C@@H](O[C@H]6OC(CNCCO)=CC[C@H]6N)[C@@H]5O)NC(=O)[C@@H](O)CCN)OC[C@]4(C)O
InChI
InChIKey=GUXPJAIJDJSSGJ-CYJQXXSXSA-N
InChI=1S/2C25H48N6O10.5H2O4S/c2*1-25(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;5*1-5(2,3)4/h2*3,13-21,23-24,29-30,32-35,37H,4-11,26-28H2,1-2H3,(H,31,36);5*(H2,1,2,3,4)/t2*13-,14+,15-,16+,17+,18-,19-,20+,21-,23-,24-,25+;;;;;/m11...../s1
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2363135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/30511766 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | ZEMDRI Approved UseZEMDRI 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 Date2018 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse events |
---|---|---|
15 mg/kg 1 times / day multiple, intravenous MTD Dose: 15 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 15 mg/kg, 1 times / day Sources: |
healthy, 18 to 65 years n = 15 Health Status: healthy Age Group: 18 to 65 years Population Size: 15 Sources: |
Other AEs: Hypotension... Other AEs: Hypotension (grade 1-2) Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
Other AEs: Abdominal pain, Nausea... Other AEs: Abdominal pain (1.7%) Sources: Nausea (10.5%) Dizziness (8.8%) Headache (7%) Hypoesthesia (17.5%) Flushing (1.7%) |
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 n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Disc. AE: Vertigo, Dizziness... AEs leading to discontinuation/dose reduction: Vertigo (1.3%) Sources: Dizziness (2.7%) Azotaemia (1.4%) Hypotension (1.4%) Type 2 diabetes mellitus (1.4%) |
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 n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Other AEs: Ototoxicity, Tinnitus... Other AEs: Ototoxicity (2.2%) Sources: 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 59.4 years n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 Sources: |
Disc. AE: Blood creatinine increased... AEs leading to discontinuation/dose reduction: Blood creatinine increased (0.3%) 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 59.4 years n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 Sources: |
Disc. AE: Acute kidney injury, Chronic kidney disease... AEs leading to discontinuation/dose reduction: Acute kidney injury (0.7%) Sources: Chronic kidney disease (0.3%) Metastatic neoplasm (0.3%) Metastatic uterine cancer (0.3%) Renal failure (0.3%) Renal impairment (0.3%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Hypotension | grade 1-2 | 15 mg/kg 1 times / day multiple, intravenous MTD Dose: 15 mg/kg, 1 times / day Route: intravenous Route: multiple Dose: 15 mg/kg, 1 times / day Sources: |
healthy, 18 to 65 years n = 15 Health Status: healthy Age Group: 18 to 65 years Population Size: 15 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
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 n = 57 Health Status: healthy Age Group: adult Population Size: 57 Sources: |
Vertigo | 1.3% 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 39.5 years n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Azotaemia | 1.4% 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 39.5 years n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Hypotension | 1.4% 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 39.5 years n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Type 2 diabetes mellitus | 1.4% 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 39.5 years n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Dizziness | 2.7% 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 39.5 years n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
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 n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
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 n = 74 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 39.5 years Sex: M+F Population Size: 74 Sources: |
Blood creatinine increased | 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 Sources: |
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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 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 n = 303 Health Status: unhealthy Condition: Complicated Urinary Tract Infections Age Group: mean age 59.4 years Sex: M+F Population Size: 303 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000ClinPharmR.pdf#page=96 Page: 96.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000ClinPharmR.pdf#page=96 Page: 96.0 |
no |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210303Orig1s000PharmR.pdf#page=14 Page: 14.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Synthesis and spectrum of the neoglycoside ACHN-490. | 2010 Nov |
|
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.
Plazomicin (ACHN-490) inhibited the growth of AG-resistant Enterobacteriaceae (MIC(90), ≤4 μg/ml), with the exception of Proteus mirabilis and indole-positive Proteae (MIC(90), 8 μg/ml and 16 μg/ml, respectively). ACHN-490 was more active alone in vitro against Pseudomonas aeruginosa and Acinetobacter baumannii isolates with AG-modifying enzymes than against those with altered permeability/efflux. The MIC(90) of ACHN-490 against AG-resistant staphylococci was 2 μg/ml.
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A78L6MT746
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100000178212
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AB-51
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CHEMBL1650559
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DTXSID60160452
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ACTIVE MOIETY
SUBSTANCE RECORD