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
Logarithm of the Partition Coefficient (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 []
Absorption Cmax
The maximum plasma concentration (Cmax) of drug is 73.7 +/- 19.7 mg/L []
Clearance
The total body clearance of drug is 4.5 L/h []
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 []
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) []
Unbound Fraction
The unbound fraction of drug in plasma is 0.84% [3]
Vd
The volume of distribution (Vd) of drug is 17.9 L []
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
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Aminoglycoside O-phosphotransferase (aphA6) DESGYWE G9FRK8_PROST Substrate [4]
Aminoglycoside acetyltransferase (aac) DE69QHT AAC2_PROST Substrate [4]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

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] [5]
Inotersen DMJ93CT Major Increased risk of nephrotoxicity by the combination of Plazomicin and Inotersen. Amyloidosis [5D00] [6]
Atracurium DM42HXN Major Additive neuromuscular blocking effects by the combination of Plazomicin and Atracurium. Corneal disease [9A76-9A78] [7]
Givosiran DM5PFIJ Moderate Increased risk of nephrotoxicity by the combination of Plazomicin and Givosiran. Inborn porphyrin/heme metabolism error [5C58] [5]
Choline salicylate DM8P137 Moderate Increased risk of nephrotoxicity by the combination of Plazomicin and Choline salicylate. Postoperative inflammation [1A00-CA43] [8]

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
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Plazomicin 500 mg/10 ml Injection 500 mg/10 ml Injection Intravenous
Jump to Detail Pharmaceutical Formulation Page of This Drug

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 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Plazomicin retains antibiotic activity against most aminoglycoside modifying enzymes. ACS Infect Dis. 2018 Jun 8;4(6):980-987.
5 Cerner Multum, Inc. "Australian Product Information.".
6 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
7 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]
8 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]