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
SMILES
CCC(CC)[C@H](NC(C)=O)[C@@H]1[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
| Molecular Formula | C15H28N4O4 |
| Molecular Weight | 328.4072 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator'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
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: UNIPROT: O91745 (Neuraminidase) Sources: http://www.ncbi.nlm.nih.gov/pubmed/24080660 |
0.08 nM [IC50] | ||
Target ID: WP3430 Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=14715540 |
0.22 nM [EC50] | ||
Target ID: WP3214 Sources: http://www.ncbi.nlm.nih.gov/pubmed/23759505 |
0.045 nM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | RAPIVAB Approved UseRAPIVAB 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 Date2014 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
46800 ng/mL |
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 |
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
20 h |
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 |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
70% |
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 Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
Other AEs: Leukopenia, Neutropenia... Other AEs: Leukopenia (42.9%) Sources: Neutropenia (14.3%) Hyperglycemia (42.9%) Hypertension (28.6%) AST increased (14.3%) ALT increased (14.3%) Diarrhea (14.3%) |
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: |
healthy, adult |
|
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: |
healthy, adult |
|
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: |
healthy, adult Health Status: healthy Age Group: adult Sex: unknown Sources: |
|
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: |
healthy, adult |
|
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: |
healthy, adult |
|
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Lymphadenopathy, Gingival pain... AEs leading to discontinuation/dose reduction: Lymphadenopathy (<1%) Sources: Gingival pain (<1%) Salivary gland pain (<1%) Rash (<1%) |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Alanine aminotransferase, Creatine phosphokinase... Other AEs: Alanine aminotransferase (grade 2-4, 3%) Sources: Creatine phosphokinase (grade 2-4, 4%) Neutrophils (grade 2-4, 8%) |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Serum glucose... Other AEs: Serum glucose (grade 2-4, 5%) Sources: |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Abdominal pain upper, Arthralgia... AEs leading to discontinuation/dose reduction: Abdominal pain upper (<1%) Sources: Arthralgia (<1%) Drug eruption (<1%) Eczema (<1%) Rash (<1%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| ALT increased | 14.3% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| AST increased | 14.3% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Diarrhea | 14.3% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Neutropenia | 14.3% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Hypertension | 28.6% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Hyperglycemia | 42.9% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Leukopenia | 42.9% | 11.4 mg/kg 1 times / day steady, intravenous Dose: 11.4 mg/kg, 1 times / day Route: intravenous Route: steady Dose: 11.4 mg/kg, 1 times / day Sources: |
unhealthy, 2.4-9.8 years Health Status: unhealthy Age Group: 2.4-9.8 years Sex: M+F Sources: |
| Gingival pain | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Lymphadenopathy | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Rash | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Salivary gland pain | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Alanine aminotransferase | grade 2-4, 3% | 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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Creatine phosphokinase | grade 2-4, 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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Neutrophils | grade 2-4, 8% | 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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Serum glucose | grade 2-4, 5% | 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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Abdominal pain upper | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Arthralgia | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Drug eruption | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Eczema | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Rash | <1% Disc. AE |
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: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| A QSAR study on influenza neuraminidase inhibitors. | 2006-02-15 |
|
| Inhibition of influenza virus infections in immunosuppressed mice with orally administered peramivir (BCX-1812). | 2003-09 |
|
| Comparison of colorimetric, fluorometric, and visual methods for determining anti-influenza (H1N1 and H3N2) virus activities and toxicities of compounds. | 2002-10 |
|
| Peramivir (BCX-1812, RWJ-270201): potential new therapy for influenza. | 2002-06 |
|
| Structural studies of the resistance of influenza virus neuramindase to inhibitors. | 2002-05-23 |
|
| Combination treatment of influenza A virus infections in cell culture and in mice with the cyclopentane neuraminidase inhibitor RWJ-270201 and ribavirin. | 2002-05 |
|
| In vitro characterization of A-315675, a highly potent inhibitor of A and B strain influenza virus neuraminidases and influenza virus replication. | 2002-04 |
|
| Systematic structure-based design and stereoselective synthesis of novel multisubstituted cyclopentane derivatives with potent antiinfluenza activity. | 2001-12-06 |
|
| Comparison of the activities of zanamivir, oseltamivir, and RWJ-270201 against clinical isolates of influenza virus and neuraminidase inhibitor-resistant variants. | 2001-12 |
|
| Characterization of an influenza A (H3N2) virus resistant to the cyclopentane neuraminidase inhibitor RWJ-270201. | 2001-12 |
|
| Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses. | 2001-10 |
|
| Influence of virus strain, challenge dose, and time of therapy initiation on the in vivo influenza inhibitory effects of RWJ-270201. | 2001-09 |
|
| Primary immune system effects of the orally administered cyclopentane neuraminidase inhibitor RWJ-270201 in influenza virus-infected mice. | 2001-06 |
|
| Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir. | 2001-04 |
|
| In vivo influenza virus-inhibitory effects of the cyclopentane neuraminidase inhibitor RJW-270201. | 2001-03 |
|
| Cyclopentane neuraminidase inhibitors with potent in vitro anti-influenza virus activities. | 2001-03 |
|
| BCX-1812 (RWJ-270201): discovery of a novel, highly potent, orally active, and selective influenza neuraminidase inhibitor through structure-based drug design. | 2000-09-21 |
Patents
Sample Use Guides
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
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=14715540
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.
| Substance Class |
Chemical
Created
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| Record UNII |
9ZS94HQO3B
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Validated (UNII)
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SUB32136
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100000124542
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m8534
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8184
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PERAMIVIR
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DTXSID10904727
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C175841
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1598096
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EXCRETED UNCHANGED |
URINE
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BINDER->LIGAND |
In vitro, human plasma protein binding was determined to be low (<18%) across a range of peramivir concentrations (10-1000 ng/mL) with no partitioning into red blood cells (Study DM99362).
BINDING
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SOLVATE->ANHYDROUS |
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TARGET ORGANISM->INHIBITOR |
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SALT/SOLVATE -> PARENT |
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TARGET ORGANISM->INHIBITOR |
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ACTIVE MOIETY |
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| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Biological Half-life | PHARMACOKINETIC |
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SINGLE DOSE |
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| Volume of Distribution | PHARMACOKINETIC |
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| Tmax | PHARMACOKINETIC |
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INTRAVENOUS ADMINISTRATION |
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