Details of the Drug

General Information of Drug (ID: DMKMBES)

Drug Name

Plazomicin

Synonyms

ACHN-490; UNII-LYO9XZ250J; 1154757-24-0; LYO9XZ250J; Plazomicin [USAN:INN]; Plazomicin (USAN); ZINC68150640; DB12615; D10151; D-Streptamine,

Indication

Disease Entry	ICD 11	Status	REF
Bronchitis	CA20	Approved	[1]
Prostate disease	GA91	Approved	[1]
Urinary tract infection	GC08	Approved	[1]
Pancreatic cancer	2C10	Phase 3	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

592.7

Topological Polar Surface Area (xlogp)

-6.2

Rotatable Bond Count (rotbonds)

13

Hydrogen Bond Donor Count (hbonddonor)

11

Hydrogen Bond Acceptor Count (hbondacc)

15

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 257 +/- 67.0 mgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 73.7 +/- 19.7 mg/L [3]
Clearance: The total body clearance of drug is 4.5 L/h [4]
Elimination: Plazomicin predominantly undergoes renal excretion, where 56% of the total administered drug was recovered in the urine within 4 hours following a single 15 mg/kg IV dose of radiolabeled plazomicin in healthy subjects [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 3.5 +/- 0.5 hours (in healthy adults with normal renal function receiving 15 mg/kg plazomicin via intravenous infusion) [3]
Unbound Fraction: The unbound fraction of drug in plasma is 0.84% [5]
Vd: The volume of distribution (Vd) of drug is 17.9 L [4]

Chemical Identifiers

Formula: C25H48N6O10
IUPAC Name: (2S)-4-amino-N-[(1R,2S,3S,4R,5S)-5-amino-4-[[(2S,3R)-3-amino-6-[(2-hydroxyethylamino)methyl]-3,4-dihydro-2H-pyran-2-yl]oxy]-2-[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy-3-hydroxycyclohexyl]-2-hydroxybutanamide
Canonical SMILES: C[C@@]1(CO[C@@H]([C@@H]([C@H]1NC)O)O[C@H]2[C@@H](C[C@@H]([C@H]([C@@H]2O)O[C@@H]3[C@@H](CC=C(O3)CNCCO)N)N)NC(=O)[C@H](CCN)O)O
InChI: 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
InChIKey: IYDYFVUFSPQPPV-PEXOCOHZSA-N

Cross-matching ID

PubChem CID: 42613186
CAS Number: 1154757-24-0
DrugBank ID: DB12615
TTD ID: D0E6BB
INTEDE ID: DR2136
ACDINA ID: D01346

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Mitochondrial rRNA methyltransferase 2 (MRM2)	TTUQ7WN	MRM2_HUMAN	Inhibitor	[1]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Aminoglycoside O-phosphotransferase (aphA6)	DESGYWE	G9FRK8_PROST	Substrate	[6]
Aminoglycoside acetyltransferase (aac)	DE69QHT	AAC2_PROST	Substrate	[6]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Plazomicin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Decreased renal excretion of Plazomicin caused by Remdesivir mediated nephrotoxicity.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Inotersen	DMJ93CT	Major	Increased risk of nephrotoxicity by the combination of Plazomicin and Inotersen.	Amyloidosis [5D00]	[8]
Atracurium	DM42HXN	Major	Additive neuromuscular blocking effects by the combination of Plazomicin and Atracurium.	Corneal disease [9A76-9A78]	[9]
Givosiran	DM5PFIJ	Moderate	Increased risk of nephrotoxicity by the combination of Plazomicin and Givosiran.	Inborn porphyrin/heme metabolism error [5C58]	[7]
Choline salicylate	DM8P137	Moderate	Increased risk of nephrotoxicity by the combination of Plazomicin and Choline salicylate.	Postoperative inflammation [1A00-CA43]	[10]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium hydroxide	E00234	14798	Alkalizing agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Plazomicin 500 mg/10 ml Injection	500 mg/10 ml	Injection	Intravenous

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References

1	In vitro activity of plazomicin against -lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE).J Antimicrob Chemother. 2017 Oct 1;72(10):2792-2795.
2	ClinicalTrials.gov (NCT01970371) A Study of Plazomicin Compared With Colistin in Patients With Infection Due to Carbapenem-Resistant Enterobacteriaceae (CRE). U.S. National Institutes of Health.
3	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
4	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
5	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
6	Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis. 2018 Jun 8;4(6):980-987.
7	Cerner Multum, Inc. "Australian Product Information.".
8	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
9	Burkett L, Bikhazi GB, Thomas KC Jr, Rosenthal DA, Wirta MG, Foldes FF "Mutual potentiation of the neuromuscular effects of antibiotics and relaxants." Anesth Analg 58 (1979): 107-15. [PMID: 571233]
10	Farag MM, Mikhail MR, Abdel-Meguid E, Abdel-Tawab S "Assessment of gentamicin-induced nephrotoxicity in rats treated with low doses of ibuprofen and diclofenac sodium." Clin Sci 91 (1996): 187-91. [PMID: 8795442]