PERAMIVIR ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H28N4O4
Molecular Weight	328.4072
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]1([C@@H](NC(C)=O)C(CC)CC)[C@H](O)[C@H](C[C@H]1NC(N)=N)C(O)=O

InChI

InChIKey=XRQDFNLINLXZLB-CKIKVBCHSA-N

InChI=1S/C15H28N4O4/c1-4-8(5-2)12(18-7(3)20)11-10(19-15(16)17)6-9(13(11)21)14(22)23/h8-13,21H,4-6H2,1-3H3,(H,18,20)(H,22,23)(H4,16,17,19)/t9-,10+,11+,12-,13+/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf
Curator's Comment: description was created based on several sources, including https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7fdedaec-9e53-4a37-a4e4-a301c8a251b8; http://www.rxlist.com/script/main/art.asp?articlekey=185939

Peramivir is a transition-state analogue and a potent, specific influenza viral neuraminidase inhibitor. Rapivab (peramivir injection) is indicated for the treatment of acute uncomplicated influenza in patients 18 years and older who have been symptomatic for no more than 2 days. Efficacy of Rapivab is based on clinical trials in which the predominant influenza virus type was influenza A and a limited number of subjects infected with influenza B virus were enrolled. Since influenza viruses change over time emergence of resistance substitutions could decrease drug effectiveness. Other factors such as changes in viral virulence might also diminish clinical benefit of antiviral drug. Efficacy could not be established in patients with serious influenza requiring hospitalization.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
UNIPROT: O91745 (Neuraminidase) 3 Target ID: UNIPROT: O91745 (Neuraminidase) Sources: http://www.ncbi.nlm.nih.gov/pubmed/24080660	Inhibitor 8297	0.08 nM [IC50]
Influenza Infection 3 Target ID: WP3430 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=14715540	Inhibitor 8297	0.22 nM [EC50]
Influenza A virus infection 3 Target ID: WP3214 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23759505	Inhibitor 8297	0.045 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Influenza virus infections 33 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf	Primary		Approved 8429	RAPIVAB Approved Use RAPIVAB is indicated for the treatment of acute uncomplicated influenza in patients 18 years and older who have been symptomatic for no more than 2 days. Launch Date 2014

C_max

Value	Dose	Co-administered	Analyte	Population
46800 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf	600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PERAMIVIR ANHYDROUS serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
102700 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf	600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PERAMIVIR ANHYDROUS serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
20 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf	600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PERAMIVIR ANHYDROUS serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
70% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf	600 mg single, intravenous dose: 600 mg route of administration: Intravenous experiment type: SINGLE co-administered:		PERAMIVIR ANHYDROUS serum	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
11.4 mg/kg 1 times / day steady, intravenous (median) Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836703/ Page: 500	unhealthy, 2.4-9.8 years n = 7 Health Status: unhealthy Condition: H1N1 Age Group: 2.4-9.8 years Sex: M+F Population Size: 7 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836703/ Page: 500	Other AEs: Leukopenia, Neutropenia... Other AEs: Leukopenia (42.9%) Neutropenia (14.3%) Hyperglycemia (42.9%) Hypertension (28.6%) AST increased (14.3%) ALT increased (14.3%) Diarrhea (14.3%) Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836703/ Page: 500
400 mg 2 times / day multiple, intravenous Highest studied dose Dose: 400 mg, 2 times / day Route: intravenous Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/	healthy, adult Health Status: healthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/	Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/
400 mg 2 times / day multiple, intravenous Highest studied dose Dose: 400 mg, 2 times / day Route: intravenous Route: multiple Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/	healthy, adult Health Status: healthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/	Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/
600 mg 1 times / day multiple, intramuscular Highest studied dose Dose: 600 mg, 1 times / day Route: intramuscular Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 60	healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 60	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 60
800 mg 1 times / day multiple, intravenous Highest studied dose Dose: 800 mg, 1 times / day Route: intravenous Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/	healthy, adult Health Status: healthy Age Group: adult Sex: M Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/	Sources: https://pubmed.ncbi.nlm.nih.gov/27805571/
800 mg 1 times / day multiple, intravenous Highest studied dose Dose: 800 mg, 1 times / day Route: intravenous Route: multiple Dose: 800 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/	healthy, adult Health Status: healthy Age Group: adult Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/	Sources: https://pubmed.ncbi.nlm.nih.gov/27317305/
300 mg 1 times / day multiple, intravenous Minumum effective dose Dose: 300 mg, 1 times / day Route: intravenous Route: multiple Dose: 300 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98	unhealthy, adult n = 363 Health Status: unhealthy Condition: acute uncomplicated influenza Age Group: adult Sex: unknown Population Size: 363 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98	Disc. AE: Lymphadenopathy, Gingival pain... AEs leading to discontinuation/dose reduction: Lymphadenopathy (<1%) Gingival pain (<1%) Salivary gland pain (<1%) Rash (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98
600 mg 1 times / day multiple, intravenous Recommended Dose: 600 mg, 1 times / day Route: intravenous Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4	unhealthy, adult n = 654 Health Status: unhealthy Condition: H1N1 Age Group: adult Sex: unknown Population Size: 654 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4	Other AEs: Alanine aminotransferase, Creatine phosphokinase... Other AEs: Alanine aminotransferase (grade 2-4, 3%) Creatine phosphokinase (grade 2-4, 4%) Neutrophils (grade 2-4, 8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4
600 mg 1 times / day multiple, intravenous Recommended Dose: 600 mg, 1 times / day Route: intravenous Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4	unhealthy, adult n = 660 Health Status: unhealthy Condition: H1N1 Age Group: adult Sex: unknown Population Size: 660 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4	Other AEs: Serum glucose... Other AEs: Serum glucose (grade 2-4, 5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206426lbl.pdf Page: 4
600 mg 1 times / day multiple, intravenous Recommended Dose: 600 mg, 1 times / day Route: intravenous Route: multiple Dose: 600 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98	unhealthy, adult n = 365 Health Status: unhealthy Condition: acute uncomplicated influenza Age Group: adult Sex: unknown Population Size: 365 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98	Disc. AE: Abdominal pain upper, Arthralgia... AEs leading to discontinuation/dose reduction: Abdominal pain upper (<1%) Arthralgia (<1%) Drug eruption (<1%) Eczema (<1%) Rash (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/206426Orig1s000ClinPharmR.pdf Page: 98

AEs

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA00C6EE	https://www.aablocks.com/goods/Goods/detail?id=AA00C6EE
AK Scientific, Inc. (AKSCI)	66630	http://www.aksci.com/item_detail.php?cat=66630
Achemtek	0102-014544	http://www.achemtek.com/330600-85-6
Acorn PharmaTech	ACN-028788	http://www.acornpharmatech.com/
Active Biopharma	ABP000969	http://www.activebiopharma.com/229614-55-5
Adooq BioScience	A11124	https://www.adooq.com/peramivir.html
Alsachim	2957	http://www.alsachim.com/product-C4029-glo.bal-view.html
ApexBio Technology	A3709	http://www.apexbt.com/peramivir-20402.html
AstaTech, Inc.	67953	http://www.astatechinc.com/CPSResult.php?CRNO=14007
Aurora Fine Chemicals LLC	A13.110.340	http://online.aurorafinechemicals.com/info?ID=A13.110.340
AvaChem Scientific	3036	http://www.avachem.com/productSearch.asp?3036
BLD Pharm	BD147150	http://www.bldpharm.com/products/330600-85-6.html
BioCrick	BCC1846	http://www.biocrick.com/Peramivir-BCC1846.html
Chem Scene	CS-0638	http://www.chemscene.com/330600-85-6.html
ChemMol	30115938	http://www.chemmol.com/chemmol/30115938.html
ChemMol	99063194	http://www.chemmol.com/chemmol/99063194.html
Chemspace	CSSB00016988245	https://chem-space.com/CSSB00016988245
DC Chemicals	DCAPI1121	http://www.dcchemicals.com//product_show-Peramivir.html
Hairui	HR118227	http://www.hairuichem.com/en/product/229614-55-5.html
Lab Network	LN00199254	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00199254
Matrix Scientific	97285	https://www.matrixscientific.com/097285.html
MedChem Express	HY-17015A	https://www.medchemexpress.com/peramivir.html
MuseChem	I012304	https://www.musechem.com/product/I012304.html
OChem	26458	http://www.ocheminc.com/index.php?act=psearch&pid=600P856
Oakwood	234978	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=115977&ExtHyperLink=1
Renno Tech	RL02720	http://www.rennotech.com/product_show.asp?id=2969
Renno Tech	RL03191	http://www.rennotech.com/product_show.asp?id=3440
Smolecule	S006020	http://www.smolecule.com/products/s006020
Smolecule	S539024	http://www.smolecule.com/products/s539024
Smolecule	S794776	https://www.smolecule.com/products/s794776
THE BioTek	bt-255076	https://www.thebiotek.com/product/inhibitors/bt-255076
THE BioTek	bt-279105	https://www.thebiotek.com/product/inhibitors/bt-279105
THE BioTek	bt-429681	https://www.thebiotek.com/product/others/bt-429681
THE BioTek	bt-459453	https://www.thebiotek.com/product/others/bt-459453
TripleBond	CP0131	http://www.triplebond-canada.com/prod/1542/
abcr GmbH	AB459983	http://www.abcr.com/shop/en/AB459983
eNovation Chemicals	D486401	https://www.enovationchem.com/ProductDetails.asp?ProductID=D486401
eNovation Chemicals	D514547	https://www.enovationchem.com/ProductDetails.asp?ProductID=D514547
eNovation Chemicals	D679637	https://www.enovationchem.com/ProductDetails.asp?ProductID=D679637
eNovation Chemicals	Y0974045	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0974045
eNovation Chemicals	Y0986882	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y0986882

PubMed

Title	Date	PubMed
Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants.	2001 Dec	11709315
Characterization of an influenza A (H3N2) virus resistant to the cyclopentane neuraminidase inhibitor RWJ-270201.	2001 Dec	11675142
Primary immune system effects of the orally administered cyclopentane neuraminidase inhibitor RWJ-270201 in influenza virus-infected mice.	2001 Jun	11407315
Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses.	2001 Oct	11557461
Influence of virus strain, challenge dose, and time of therapy initiation on the in vivo influenza inhibitory effects of RWJ-270201.	2001 Sep	11448729
Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza.	2002 Jun	12036429
Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds.	2002 Oct	12367731
Inhibition of influenza virus infections in immunosuppressed mice with orally administered peramivir (BCX-1812).	2003 Sep	14516917
A QSAR study on influenza neuraminidase inhibitors.	2006 Feb 15	16213733

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of RAPIVAB in adult patients 18 years of age or older with acute uncomplicated influenza is a single 600 mg dose, administered via intravenous infusion for 15 to 30 minutes. The dose should be reduced for patients with baseline creatinine clearance below 50 mL/min to 200 mg dose (at 30-49 mL/min creatinine clearance), and 100 mg dose (at 10-29 mL/min creatinine clearance).

Route of Administration: Intravenous

In Vitro Use Guide

The concentrations of peramivir required for inhibition of influenza virus in cell culture varied with the virus strain tested. The effect of antiviral compounds on the replication of influenza viruses in MDCK cells was determined by flow cytometric analysis of virus-infected cells. The mean 50% effective concentrations (EC50 values) of peramivir were in the range of 0.045-0.071 nM), 0.065-0.07 nM and 0.215-33.58 nM for influenza A/H1N1 virus, A/H3N2 virus, and B virus strains, respectively.

Name

Type

Language

PERAMIVIR ANHYDROUS

Common Name

English

RWJ-270201

Code

English

(1S,2S,3R,4R)-3-((1S)-1-ACETYLAMINO-2-ETHYLBUTYL)-4-((AMINOIMINOMETHYL)AMINO)-2-HYDROXYCYCLOPENTANECARBOXYLIC ACID

Systematic Name

English

peramivir [INN]

Common Name

English

PERAMIVIR [MI]

Common Name

English

Code System Code Type Description

EVMPD

SUB32136