Identification

Name
Plazomicin
Accession Number
DB12615
Type
Small Molecule
Groups
Approved, Investigational
Description

Developed by Achaogen biopharmaceuticals, plazomicin is a next-generation aminoglycoside synthetically derived from Sisomicin. The structure of plazomicin was established via appending hydroxylaminobutyric acid to Sisomicin at position 1 and 2-hydroxyethyl group at position 6' [1]. It was designed to evade all clinically relevant aminoglycoside-modifying enzymes, which contribute to the main resistance mechanism for aminoglycoside therapy [1]. However, acquired resistance of aminoglycosides may arise through over expression of efflux pumps and ribosomal modification by bacteria, which results from amino acid or rRNA sequence mutations [1]. Like other aminoglycosides, plazomicin is ineffective against bacterial isolates that produce 16S rRNA methyltransferases [Label]. Plazomicin mediates the antibacterial activity against pathogens including carbapenem-resistant (CRE) and extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. It mediates the antibacterial activity by binding to bacterial 30S ribosomal subunit and inhibiting protein synthesis [Label]. On June 28th, 2018, plazomicin sulfate was approved by the FDA for use in adult patients for the treatment of complicated urinary tract infections (cUTI) including Pyelonephritis. It is marketed as Zemdri and is administered via once-daily intravenous infusion.

Structure
Thumb
Synonyms
Not Available
External IDs
ACHN 490 / ACHN-490 / ACHN490
Product Ingredients
IngredientUNIICASInChI Key
Plazomicin sulfateA78L6MT7461380078-95-4SFTBRKHJMASSAP-BGJNVEJLSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Zemdri (plazomicin)Injection500 mg/10mLIntravenousAchaogen, Inc.2018-07-16Not applicableUs
Categories
UNII
LYO9XZ250J
CAS number
1154757-24-0
Weight
Average: 592.691
Monoisotopic: 592.34319177
Chemical Formula
C25H48N6O10
InChI Key
IYDYFVUFSPQPPV-PEXOCOHZSA-N
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
IUPAC Name
(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-{[(2R,3R,4R,5R)-3,5-dihydroxy-5-methyl-4-(methylamino)oxan-2-yl]oxy}-3-hydroxycyclohexyl]-2-hydroxybutanamide
SMILES
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

Pharmacology

Indication

Plazomicin is indicated for the treatment of patients 18 years of age or older with Complicated Urinary Tract Infections (cUTI) including Pyelonephritis, who have limited or no alternative treatment options. It should only be used to treat infections that are proven or strongly suspected to be caused by susceptible microorganisms [Label].

Pharmacodynamics

Plazomicin exerts its antibacterial activity in a dose-dependent manner with a post-antibiotic effect ranging from 0.2 to 2.6 hours at 2X MIC against Enterobacteriaceae, as demonstrated by in vitro studies [Label]. In clinical trials comprising of hospitalized adult patients with cUTI (including pyelonephritis), resolution or improvement of clinical cUTI symptoms and a microbiological outcome of eradication were observed at day 5 following the first dose administration of plazomicin [Label]. Plazomicin has shown to elicit nephrotoxic, ototoxic, and neuromuscular blocking effects. In clinical trials, it did not induce any clinically relevant QTc-prolonging effects [Label].

Mechanism of action

Plazomicin exerts a bactericidal action against susceptible bacteria by binding to bacterial 30S ribosomal subunit [1]. Aminoglycosides typically bind to the ribosomal aminoacyl-tRNA site (A-site) and induce a conformational change to further facilitate the binding between the rRNA and the antibiotic [5]. This leads to codon misreading and mistranslation of mRNA during bacterial protein synthesis [5].

Plazomicin demonstrates potency against Enterobacteriaceae, including species with multidrug-resistant phenotypes such as carbapenemase-producing bacteria and isolates with resistance to all other aminoglycosides [1, 2, 3]. Its antibacterial activity is not inhibited by aminoglycoside modifying enzymes (AMEs) produced by bacteria, such as acetyltransferases (AACs), phosphotransferases (APHs), and nucleotidyltransferases (ANTs) [4]. Plazomicin was shown to be effective against Enterobacteriaceae in presence of some beta-lactamases [Label]. In clinical settings and in vivo, bacteria shown to be susceptible toward plazomicin include Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Enterobacter cloacae [Label]. Other aerobic bacteria that may be affected by plazomicin are Citrobacter freundii, Citrobacter koseri, Enterobacter aerogenes, Klebsiella oxytoca, Morganella morganii, Proteus vulgaris, Providencia stuartii, and Serratia marcescens [Label].

TargetActionsOrganism
U30S ribosomal protein S14
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S11
inhibitor
Enterobacteriaceae bacterium (strain FGI 57)
Absorption

Administration of 15 mg/kg plazomicin by 30-minute IV infusion resulted in peak plasma concentrations of 73.7 ± 19.7 μg/mL in healthy adult subjects and 51.0 ± 26.7 μg/mL in patients with complicated urinary tract infections (cUTI) [Label]. The area under the curve (AUC) were 257 ± 67.0 μg.h/mL in healthy adults and 226 ± 113 μg.h/mL in cUTI patients [Label].

Volume of distribution

The mean (±SD) volume of distribution is 17.9 (±4.8) L in healthy adults and 30.8 (±12.1) L in cUTI patients [Label].

Protein binding

The extent of plasma protein binding in humans is approximately 20% [Label]. The degree of protein binding was concentration-independent across the range tested in vitro (5 to 100 mcg/mL) [Label].

Metabolism

Plazomicin is not reported to undergo significant metabolism [Label].

Route of 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. About less than 0.2% and 89.1% of the total drug were recovered within 168 hours in feces and urine, respectively [Label].

Half life

The mean (±SD) half-life of plazomicin was 3.5 h (±0.5) in healthy adults with normal renal function receiving 15 mg/kg plazomicin via intravenous infusion [Label].

Clearance

Following administration of 15 mg/kg plazomicin by 30-minute IV infusion, the mean (±SD) total body clearance in healthy adults and cUTI patients is 4.5 (±0.9) and 5.1 (±2.01) L/h, respectively [Label].

Toxicity

In case of suspected overdose, plazomicin therapy should be discontinued with initiation of supportive care. Maintenance of glomerular filtration and careful monitoring of renal function is recommended. Hemodialysis may be used to facilitate drug elimination, and this may be especially clinically useful in patients with compromised renal function [Label].

Affected organisms
  • Pseudomonas aeruginosa
  • Escherichia coli
  • Acinetobacter
  • Enterobacter
  • Klebsiella pneumoniae
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
(4R)-limonene(4R)-limonene may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
AceclofenacAceclofenac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
AcemetacinAcemetacin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Experimental, Investigational
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be decreased when it is combined with Plazomicin.Approved
AcetyldigoxinThe serum concentration of Acetyldigoxin can be decreased when it is combined with Plazomicin.Experimental
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
AdapaleneAdapalene may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
AlclofenacAlclofenac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Withdrawn
AlcuroniumPlazomicin may increase the respiratory depressant activities of Alcuronium.Experimental
Alendronic acidPlazomicin may increase the hypocalcemic activities of Alendronic acid.Approved
AlminoprofenAlminoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
AmdinocillinThe serum concentration of Plazomicin can be decreased when it is combined with Amdinocillin.Investigational, Withdrawn
AmoxicillinThe serum concentration of Plazomicin can be decreased when it is combined with Amoxicillin.Approved, Vet Approved
Amphotericin BAmphotericin B may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
AmpicillinThe serum concentration of Plazomicin can be decreased when it is combined with Ampicillin.Approved, Vet Approved
AndrographolideAndrographolide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
AnisodamineAnisodamine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
AntipyrineAntipyrine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
ApocyninApocynin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
ApremilastApremilast may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
AspoxicillinThe serum concentration of Plazomicin can be decreased when it is combined with Aspoxicillin.Experimental
AtracuriumPlazomicin may increase the respiratory depressant activities of Atracurium.Approved, Experimental, Investigational
Atracurium besylatePlazomicin may increase the respiratory depressant activities of Atracurium besylate.Approved
AzapropazoneAzapropazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
AzelastineAzelastine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
AzidocillinThe serum concentration of Plazomicin can be decreased when it is combined with Azidocillin.Approved
AzlocillinThe serum concentration of Plazomicin can be decreased when it is combined with Azlocillin.Approved
AzosemideThe serum concentration of Plazomicin can be increased when it is combined with Azosemide.Investigational
BacampicillinThe serum concentration of Plazomicin can be decreased when it is combined with Bacampicillin.Approved, Investigational
BalsalazideBalsalazide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
BendazacBendazac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
BenorilateBenorilate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
BenoxaprofenBenoxaprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
BenzydamineBenzydamine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
BenzylpenicillinThe serum concentration of Plazomicin can be decreased when it is combined with Benzylpenicillin.Approved, Vet Approved
Benzylpenicilloyl PolylysineThe serum concentration of Plazomicin can be decreased when it is combined with Benzylpenicilloyl Polylysine.Approved
BevoniumBevonium may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Botulinum Toxin Type APlazomicin may increase the neuromuscular blocking activities of Botulinum Toxin Type A.Approved, Investigational
Botulinum Toxin Type BPlazomicin may increase the neuromuscular blocking activities of Botulinum Toxin Type B.Approved, Investigational
BromfenacBromfenac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
BucillamineBucillamine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
BufexamacBufexamac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Experimental
BumadizoneBumadizone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
BumetanideThe serum concentration of Plazomicin can be increased when it is combined with Bumetanide.Approved
CapreomycinCapreomycin may increase the neuromuscular blocking activities of Plazomicin.Approved
Carbaspirin calciumCarbaspirin calcium may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental, Investigational
CarbenicillinThe serum concentration of Plazomicin can be decreased when it is combined with Carbenicillin.Approved, Investigational
Carbenicillin indanylThe serum concentration of Plazomicin can be decreased when it is combined with Carbenicillin indanyl.Approved, Investigational
CarboplatinPlazomicin may increase the ototoxic activities of Carboplatin.Approved
CarfecillinThe serum concentration of Plazomicin can be decreased when it is combined with Carfecillin.Experimental
CarprofenCarprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved, Withdrawn
CastanospermineCastanospermine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
CefaclorCefaclor may increase the nephrotoxic activities of Plazomicin.Approved
CefamandoleCefamandole may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefbuperazoneCefbuperazone may increase the nephrotoxic activities of Plazomicin.Experimental
CefcapeneCefcapene may increase the nephrotoxic activities of Plazomicin.Experimental
CefdinirCefdinir may increase the nephrotoxic activities of Plazomicin.Approved
CefditorenCefditoren may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefepimeCefepime may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefetametCefetamet may increase the nephrotoxic activities of Plazomicin.Experimental
CefiximeCefixime may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefmenoximeCefmenoxime may increase the nephrotoxic activities of Plazomicin.Approved
CefmetazoleCefmetazole may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefminoxCefminox may increase the nephrotoxic activities of Plazomicin.Approved
CefodizimeCefodizime may increase the nephrotoxic activities of Plazomicin.Experimental
CefonicidCefonicid may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefoperazoneCefoperazone may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CeforanideCeforanide may increase the nephrotoxic activities of Plazomicin.Approved
CefotaximeCefotaxime may increase the nephrotoxic activities of Plazomicin.Approved
CefotetanCefotetan may increase the nephrotoxic activities of Plazomicin.Approved
CefotiamCefotiam may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CefoxitinCefoxitin may increase the nephrotoxic activities of Plazomicin.Approved
CefozopranCefozopran may increase the nephrotoxic activities of Plazomicin.Experimental
CefpiramideCefpiramide may increase the nephrotoxic activities of Plazomicin.Approved
CefpiromeCefpirome may increase the nephrotoxic activities of Plazomicin.Approved
CefpodoximeCefpodoxime may increase the nephrotoxic activities of Plazomicin.Approved, Vet Approved
CefprozilCefprozil may increase the nephrotoxic activities of Plazomicin.Approved
CefsulodinCefsulodin may increase the nephrotoxic activities of Plazomicin.Experimental
CeftazidimeCeftazidime may increase the nephrotoxic activities of Plazomicin.Approved
CeftibutenCeftibuten may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CeftizoximeCeftizoxime may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
CeftriaxoneCeftriaxone may increase the nephrotoxic activities of Plazomicin.Approved
CefuroximeCefuroxime may increase the nephrotoxic activities of Plazomicin.Approved
CelecoxibCelecoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
ChloroquineChloroquine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Vet Approved
ChlorthalidoneThe serum concentration of Plazomicin can be increased when it is combined with Chlorthalidone.Approved
Choline magnesium trisalicylateCholine magnesium trisalicylate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
CisatracuriumPlazomicin may increase the respiratory depressant activities of Cisatracurium.Approved
CisplatinCisplatin may increase the nephrotoxic activities of Plazomicin.Approved
Clodronic AcidPlazomicin may increase the hypocalcemic activities of Clodronic Acid.Approved, Investigational, Vet Approved
ClonixinClonixin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
CloxacillinThe serum concentration of Plazomicin can be decreased when it is combined with Cloxacillin.Approved, Investigational, Vet Approved
ColistimethatePlazomicin may increase the nephrotoxic activities of Colistimethate.Approved, Vet Approved
CurcuminCurcumin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
CyclacillinThe serum concentration of Plazomicin can be decreased when it is combined with Cyclacillin.Approved
CyclosporinePlazomicin may increase the nephrotoxic activities of Cyclosporine.Approved, Investigational, Vet Approved
CymarinThe serum concentration of Cymarin can be decreased when it is combined with Plazomicin.Experimental
DecamethoniumPlazomicin may increase the respiratory depressant activities of Decamethonium.Approved
DeslanosideThe serum concentration of Deslanoside can be decreased when it is combined with Plazomicin.Approved
DiclofenacDiclofenac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
DicloxacillinThe serum concentration of Plazomicin can be decreased when it is combined with Dicloxacillin.Approved, Investigational, Vet Approved
DifenpiramideDifenpiramide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
DiflunisalDiflunisal may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
DigitoxinThe serum concentration of Digitoxin can be decreased when it is combined with Plazomicin.Approved, Investigational
DigoxinThe serum concentration of Digoxin can be decreased when it is combined with Plazomicin.Approved
Digoxin Immune Fab (Ovine)The serum concentration of Digoxin Immune Fab (Ovine) can be decreased when it is combined with Plazomicin.Approved
Domoic AcidPlazomicin may increase the respiratory depressant activities of Domoic Acid.Experimental
DoxacuriumPlazomicin may increase the respiratory depressant activities of Doxacurium chloride.Approved
DroxicamDroxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
DuvelisibDuvelisib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
E-6201E-6201 may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
EpicillinThe serum concentration of Plazomicin can be decreased when it is combined with Epicillin.Experimental
EpirizoleEpirizole may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
Etacrynic acidThe serum concentration of Plazomicin can be increased when it is combined with Etacrynic acid.Approved, Investigational
EtanerceptEtanercept may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
EthenzamideEthenzamide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Etidronic acidPlazomicin may increase the hypocalcemic activities of Etidronic acid.Approved
EtodolacEtodolac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Vet Approved
EtofenamateEtofenamate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
EtoricoxibEtoricoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
Evening primrose oilEvening primrose oil may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational, Nutraceutical
ExisulindExisulind may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
FelbinacFelbinac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
FenbufenFenbufen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
FenoprofenFenoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
FentiazacFentiazac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
FeprazoneFeprazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Ferulic acidFerulic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
FloctafenineFloctafenine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Withdrawn
FlomoxefFlomoxef may increase the nephrotoxic activities of Plazomicin.Investigational
FlucloxacillinThe serum concentration of Plazomicin can be decreased when it is combined with Flucloxacillin.Approved, Investigational
FlunixinFlunixin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Vet Approved
FlunoxaprofenFlunoxaprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
FlurbiprofenFlurbiprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
FoscarnetFoscarnet may increase the nephrotoxic activities of Plazomicin.Approved
FurosemideThe serum concentration of Plazomicin can be increased when it is combined with Furosemide.Approved, Vet Approved
GallaminePlazomicin may increase the respiratory depressant activities of Gallamine.Experimental
Gallamine TriethiodidePlazomicin may increase the respiratory depressant activities of Gallamine Triethiodide.Approved
GitoformateThe serum concentration of Gitoformate can be decreased when it is combined with Plazomicin.Experimental
GuacetisalGuacetisal may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
HigenamineHigenamine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
HydroflumethiazideThe serum concentration of Plazomicin can be increased when it is combined with Hydroflumethiazide.Approved, Investigational
IbandronatePlazomicin may increase the hypocalcemic activities of Ibandronate.Approved, Investigational
IbuprofenIbuprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
IbuproxamIbuproxam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
IcatibantIcatibant may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
Imidazole salicylateImidazole salicylate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
IndobufenIndobufen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
IndomethacinIndomethacin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
IndoprofenIndoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
IsoxicamIsoxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
KebuzoneKebuzone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
KetoprofenKetoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
KetorolacKetorolac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
Lanatoside CThe serum concentration of Lanatoside C can be decreased when it is combined with Plazomicin.Experimental
LatamoxefLatamoxef may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
LeflunomideLeflunomide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
LisofyllineLisofylline may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
LonazolacLonazolac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
LoracarbefLoracarbef may increase the nephrotoxic activities of Plazomicin.Investigational, Withdrawn
LornoxicamLornoxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
LoxoprofenLoxoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
LumiracoxibLumiracoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
Magnesium salicylateMagnesium salicylate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
MannitolMannitol may increase the nephrotoxic activities of Plazomicin.Approved, Investigational
MasoprocolMasoprocol may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
MecamylaminePlazomicin may increase the neuromuscular blocking activities of Mecamylamine.Approved, Investigational
Meclofenamic acidMeclofenamic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
Mefenamic acidMefenamic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
MeloxicamMeloxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
MesalazineMesalazine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
MetamizoleMetamizole may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Withdrawn
MetampicillinThe serum concentration of Plazomicin can be decreased when it is combined with Metampicillin.Experimental
MethyclothiazideThe serum concentration of Plazomicin can be increased when it is combined with Methyclothiazide.Approved
MeticillinThe serum concentration of Plazomicin can be decreased when it is combined with Meticillin.Approved, Investigational
MetildigoxinThe serum concentration of Metildigoxin can be decreased when it is combined with Plazomicin.Experimental
MetocurinePlazomicin may increase the respiratory depressant activities of Metocurine.Approved
Metocurine IodidePlazomicin may increase the respiratory depressant activities of Metocurine Iodide.Approved, Withdrawn
MezlocillinThe serum concentration of Plazomicin can be decreased when it is combined with Mezlocillin.Approved, Investigational
MivacuriumPlazomicin may increase the respiratory depressant activities of Mivacurium.Approved
MizoribineMizoribine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
MofebutazoneMofebutazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Mycophenolate mofetilMycophenolate mofetil may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
Mycophenolic acidMycophenolic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
NabumetoneNabumetone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
NafamostatNafamostat may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
NafcillinThe serum concentration of Plazomicin can be decreased when it is combined with Nafcillin.Approved, Investigational
NaftifineNaftifine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
NaproxenNaproxen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
NeosaxitoxinPlazomicin may increase the respiratory depressant activities of Neosaxitoxin.Investigational
NepafenacNepafenac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
NifenazoneNifenazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Niflumic AcidNiflumic Acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
NimesulideNimesulide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Withdrawn
NitroaspirinNitroaspirin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
OleandrinThe serum concentration of Oleandrin can be decreased when it is combined with Plazomicin.Experimental, Investigational
OlopatadineOlopatadine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
OlsalazineOlsalazine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
OrgoteinOrgotein may decrease the excretion rate of Plazomicin which could result in a higher serum level.Vet Approved
OuabainThe serum concentration of Ouabain can be decreased when it is combined with Plazomicin.Approved
OxacillinThe serum concentration of Plazomicin can be decreased when it is combined with Oxacillin.Approved, Investigational
OxaprozinOxaprozin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
OxyphenbutazoneOxyphenbutazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Withdrawn
PalmidrolPalmidrol may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental, Nutraceutical
PamidronatePlazomicin may increase the hypocalcemic activities of Pamidronate.Approved
PancuroniumPlazomicin may increase the respiratory depressant activities of Pancuronium.Approved
ParecoxibParecoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
ParthenolideParthenolide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
PenamecillinThe serum concentration of Plazomicin can be decreased when it is combined with Penamecillin.Experimental
PeruvosideThe serum concentration of Peruvoside can be decreased when it is combined with Plazomicin.Experimental
PhenoxymethylpenicillinThe serum concentration of Plazomicin can be decreased when it is combined with Phenoxymethylpenicillin.Approved, Vet Approved
PhenylbutazonePhenylbutazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Vet Approved
PimecrolimusPimecrolimus may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
PipecuroniumPlazomicin may increase the respiratory depressant activities of Pipecuronium.Approved
PiperacillinThe serum concentration of Plazomicin can be decreased when it is combined with Piperacillin.Approved
PiretanideThe serum concentration of Plazomicin can be increased when it is combined with Piretanide.Approved
PirfenidonePirfenidone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
PiroxicamPiroxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
PirprofenPirprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
PivampicillinThe serum concentration of Plazomicin can be decreased when it is combined with Pivampicillin.Approved
PivmecillinamThe serum concentration of Plazomicin can be decreased when it is combined with Pivmecillinam.Approved
PranoprofenPranoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental, Investigational
Procaine benzylpenicillinThe serum concentration of Plazomicin can be decreased when it is combined with Procaine benzylpenicillin.Approved, Vet Approved
ProglumetacinProglumetacin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
PropacetamolPropacetamol may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
PropicillinThe serum concentration of Plazomicin can be decreased when it is combined with Propicillin.Experimental
PropyphenazonePropyphenazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
ProquazoneProquazone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
ProscillaridinThe serum concentration of Proscillaridin can be decreased when it is combined with Plazomicin.Experimental
PTC299PTC299 may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
PyrantelPlazomicin may increase the respiratory depressant activities of Pyrantel.Approved, Vet Approved
QuinethazoneThe serum concentration of Plazomicin can be increased when it is combined with Quinethazone.Approved
RapacuroniumPlazomicin may increase the respiratory depressant activities of Rapacuronium.Withdrawn
ResveratrolResveratrol may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Experimental, Investigational
RisedronatePlazomicin may increase the hypocalcemic activities of Risedronate.Approved, Investigational
RocuroniumPlazomicin may increase the respiratory depressant activities of Rocuronium.Approved
RofecoxibRofecoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Withdrawn
SalicylamideSalicylamide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
Salicylic acidSalicylic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Vet Approved
SalsalateSalsalate may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
SemapimodSemapimod may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
SeratrodastSeratrodast may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
SerrapeptaseSerrapeptase may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
SRT501SRT501 may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
SuccinylcholinePlazomicin may increase the respiratory depressant activities of Succinylcholine.Approved
SulbenicillinThe serum concentration of Plazomicin can be decreased when it is combined with Sulbenicillin.Experimental
SulfasalazineSulfasalazine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
SulindacSulindac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
SultamicillinThe serum concentration of Plazomicin can be decreased when it is combined with Sultamicillin.Approved, Investigational
SuprofenSuprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Withdrawn
SuxibuzoneSuxibuzone may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
TalampicillinThe serum concentration of Plazomicin can be decreased when it is combined with Talampicillin.Experimental
TarenflurbilTarenflurbil may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
Technetium Tc-99m etidronatePlazomicin may increase the hypocalcemic activities of Technetium Tc-99m etidronate.Approved
Technetium Tc-99m medronatePlazomicin may increase the hypocalcemic activities of Technetium Tc-99m medronate.Approved
TenidapTenidap may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
Tenofovir disoproxilThe serum concentration of Plazomicin can be increased when it is combined with Tenofovir disoproxil.Approved, Investigational
TenoxicamTenoxicam may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
TepoxalinTepoxalin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Vet Approved
TeriflunomideTeriflunomide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
Tiaprofenic acidTiaprofenic acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
TicarcillinThe serum concentration of Plazomicin can be decreased when it is combined with Ticarcillin.Approved, Investigational, Vet Approved
Tiludronic acidPlazomicin may increase the hypocalcemic activities of Tiludronic acid.Approved, Investigational, Vet Approved
TinoridineTinoridine may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
Tolfenamic AcidTolfenamic Acid may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
TolmetinTolmetin may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved
TorasemideThe serum concentration of Plazomicin can be increased when it is combined with Torasemide.Approved
TranilastTranilast may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
TribenosideTribenoside may decrease the excretion rate of Plazomicin which could result in a higher serum level.Experimental
TrichlormethiazideThe serum concentration of Plazomicin can be increased when it is combined with Trichlormethiazide.Approved, Vet Approved
TriptolideTriptolide may decrease the excretion rate of Plazomicin which could result in a higher serum level.Investigational
TubocurarinePlazomicin may increase the respiratory depressant activities of Tubocurarine.Approved
ValdecoxibValdecoxib may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Withdrawn
VancomycinVancomycin may increase the nephrotoxic activities of Plazomicin.Approved
VecuroniumPlazomicin may increase the respiratory depressant activities of Vecuronium.Approved
ZaltoprofenZaltoprofen may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational
ZileutonZileuton may decrease the excretion rate of Plazomicin which could result in a higher serum level.Approved, Investigational, Withdrawn
Zoledronic acidPlazomicin may increase the hypocalcemic activities of Zoledronic acid.Approved
ZomepiracZomepirac may decrease the excretion rate of Plazomicin which could result in a higher serum level.Withdrawn
Food Interactions
Not Available

References

General References
  1. Karaiskos I, Souli M, Giamarellou H: Plazomicin: an investigational therapy for the treatment of urinary tract infections. Expert Opin Investig Drugs. 2015;24(11):1501-11. doi: 10.1517/13543784.2015.1095180. Epub 2015 Sep 30. [PubMed:26419762]
  2. Denervaud-Tendon V, Poirel L, Connolly LE, Krause KM, Nordmann P: Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates. J Antimicrob Chemother. 2017 Oct 1;72(10):2787-2791. doi: 10.1093/jac/dkx239. [PubMed:29091226]
  3. Zhang Y, Kashikar A, Bush K: In vitro activity of plazomicin against beta-lactamase-producing carbapenem-resistant Enterobacteriaceae (CRE). J Antimicrob Chemother. 2017 Oct 1;72(10):2792-2795. doi: 10.1093/jac/dkx261. [PubMed:29091224]
  4. Lopez-Diaz MD, Culebras E, Rodriguez-Avial I, Rios E, Vinuela-Prieto JM, Picazo JJ, Rodriguez-Avial C: Plazomicin Activity against 346 Extended-Spectrum-beta-Lactamase/AmpC-Producing Escherichia coli Urinary Isolates in Relation to Aminoglycoside-Modifying Enzymes. Antimicrob Agents Chemother. 2017 Jan 24;61(2). pii: AAC.02454-16. doi: 10.1128/AAC.02454-16. Print 2017 Feb. [PubMed:27919895]
  5. Dlugosz M, Trylska J: Aminoglycoside association pathways with the 30S ribosomal subunit. J Phys Chem B. 2009 May 21;113(20):7322-30. doi: 10.1021/jp8112914. [PubMed:19438282]
External Links
PubChem Compound
42613186
PubChem Substance
347828829
ChemSpider
26390008
ChEMBL
CHEMBL1650559
HET
EDS
Wikipedia
Plazomicin
PDB Entries
6cd7
FDA label
Download (436 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentCardiac Effects in Normal Healthy Volunteers1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentImpaired Renal Function1
2CompletedTreatmentAcute Pyelonephritis / Complicated Urinary Tract Infections1
3CompletedTreatmentAcute Pyelonephritis (AP) Due to CRE / Bloodstream Infections (BSI) Due to CRE / Complicated Urinary Tract Infection (cUTI) Due to CRE / Hospital-Acquired Bacterial Pneumonia (HABP) Due to CRE / Ventilator-Associated Bacterial Pneumonia (VABP) Due to CRE1
3CompletedTreatmentAcute Pyelonephritis / Complicated Urinary Tract Infections1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntravenous500 mg/10mL
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility12.3 mg/mLALOGPS
logP-2.2ALOGPS
logP-6.1ChemAxon
logS-1.7ALOGPS
pKa (Strongest Acidic)12.48ChemAxon
pKa (Strongest Basic)9.89ChemAxon
Physiological Charge5ChemAxon
Hydrogen Acceptor Count15ChemAxon
Hydrogen Donor Count11ChemAxon
Polar Surface Area269.29 Å2ChemAxon
Rotatable Bond Count13ChemAxon
Refractivity145.09 m3·mol-1ChemAxon
Polarizability62.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as gamma amino acids and derivatives. These are amino acids having a (-NH2) group attached to the gamma carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Gamma amino acids and derivatives
Alternative Parents
O-glycosyl compounds / Aminocyclitols and derivatives / Aminosaccharides / Cyclohexylamines / Cyclohexanols / Oxanes / N-acyl amines / Monosaccharides / Tertiary alcohols / 1,3-aminoalcohols
show 11 more
Substituents
Gamma amino acid or derivatives / Glycosyl compound / O-glycosyl compound / Aminocyclitol or derivatives / Cyclohexanol / Cyclohexylamine / Amino saccharide / Cyclitol or derivatives / Fatty amide / Fatty acyl
show 30 more
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Structural constituent of ribosome
Specific Function
Binds 16S rRNA, required for the assembly of 30S particles and may also be responsible for determining the conformation of the 16S rRNA at the A site.
Gene Name
rpsN
Uniprot ID
P0AG59
Uniprot Name
30S ribosomal protein S14
Molecular Weight
11580.36 Da
Kind
Protein
Organism
Enterobacteriaceae bacterium (strain FGI 57)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Located on the platform of the 30S subunit, it bridges several disparate RNA helices of the 16S rRNA. Forms part of the Shine-Dalgarno cleft in the 70S ribosome.
Specific Function
Rrna binding
Gene Name
rpsK
Uniprot ID
L0LZJ6
Uniprot Name
30S ribosomal protein S11
Molecular Weight
13858.85 Da
References
  1. Denervaud-Tendon V, Poirel L, Connolly LE, Krause KM, Nordmann P: Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates. J Antimicrob Chemother. 2017 Oct 1;72(10):2787-2791. doi: 10.1093/jac/dkx239. [PubMed:29091226]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Inhibition of MATE1 renal transporter was observed in vitro with an IC50 value of 1300 mcg/mL.
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Inhibition of MATE2-K renal transporter was observed in vitro with an IC50 value of 338 mcg/mL.
General Function
Drug transmembrane transporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide, metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acy...
Gene Name
SLC47A2
Uniprot ID
Q86VL8
Uniprot Name
Multidrug and toxin extrusion protein 2
Molecular Weight
65083.915 Da

Drug created on October 20, 2016 17:13 / Updated on July 02, 2018 21:03