General
Preferred name
OSELTAMIVIR
Synonyms
OSELTAMIVIR PHOSPHATE ()
GS 4104 ()
Tamiflu ()
Oseltamivir phosphate ()
Oseltamivir (phosphate) ()
oseltamivir phosphate (tablet) ()
GS 4104 (phosphate) ()
RO 64-0796/002 ()
Ro-64-0796-002 ()
Oseltamiviri phosphas ()
Oseltamivir (as phosphate) ()
Agucort ()
RO-64-0796 ()
GS-4104 ()
GS4104 ()
GS-4071 ETHYL ESTER ()
oseltamivir carboxylate ()
RO64-0796 ()
Ro-640796 ()
RO 640796 ()
Oseltamivir ()
P&D ID
PD010174
CAS
196618-13-0
204255-11-8
Tags
prodrug
natural product
drug
available
Approved by
EMA
FDA
First approval
1999
Drug Status
approved
Drug indication
Influenza virus infection
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
PHARMACODYNAMICS Oseltamivir is a prodrug (usually administered as phosphate) [F3094, F3097, L5161, F3115]. Once administered into the patient, it is extensively hydrolyzed by esterases located primarily in the liver to the active metabolite, the free carboxylate of oseltamivir [F3094, F3097, L5161, F3115]. In general, the specific pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that a variety of clinically significant pharmacodynamic and/or pharmacokinetic interactions may be unlikely [F3097, L5161].
INDICATION In general, oseltamivir is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours [F3094]. In particular, this agent is indicated in adults and children including full-term neonates who present with symptoms typical of influenza when influenza virus is circulating in the community [F3097]. Efficacy has been demonstrated when treatment is initiated within two days of the first onset of symptoms [F3097]. Oseltamivir is also indicated for the prophylaxis of influenza in patients one year and older [F3094]. Specifically, post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community qualifies for such prophylactic therapy [F3097]. Moreover, oseltamivir would only be indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak [F3097].
ROE Absorbed oseltamivir is primarily (> 90 %) eliminated by conversion to oseltamivir carboxylate [F3094, F3097, L5161, F3115]. It is not further metabolized and is eliminated in the urine [F3094, F3097, L5161, F3115]. The active metabolite oseltamivir carboxylate is eliminated entirely by renal excretion [F3094, F3097, L5161, F3115]. As renal clearance (18.8 l/h) exceeds glomerular filtration rate (7.5 l/h) indicating that tubular secretion occurs in addition to glomerular filtration [F3094, F3097, L5161, F3115]. Less than 20 % of an oral radiolabelled dose is eliminated in faeces [F3094, F3097, L5161, F3115].
HALF-LIFE Plasma concentrations of oseltamivir declined with a half-life of 1 to 3 hours in most subjects after oral administration, although plasma concentrations of oseltamivir carboxylate declined with a half-life of 6 to 10 hours in most subjects after oral administration [F3094, F3097].
METABOLISM Oseltamivir is extensively converted to the active metabolite, oseltamivir carboxylate, by esterases located predominantly in the liver [F3094, F3097, L5161, F3115]. Oseltamivir carboxylate is not further metabolized [F3094, F3097, L5161, F3115]. Neither oseltamivir nor oseltamivir carboxylate is a substrate for, or inhibitor of, cytochrome P450 isoforms [F3094, F3097, L5161, F3115]. No phase 2 conjugates of either compound have been identified in vivo [F3094, F3097, L5161, F3115].
ABSORPTION Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate (pro-drug) and is extensively converted by predominantly hepatic esterases to the active metabolite (oseltamivir carboxylate) [F3094, F3097, L5161, F3115]. At least 75 % of an oral dose reaches the systemic circulation as the active metabolite [F3094, F3097, L5161, F3115]. Exposure to the pro-drug is less than 5 % relative to the active metabolite [F3094, F3097, L5161, F3115]. Plasma concentrations of both pro-drug and active metabolite are proportional to dose and are unaffected by co-administration with food [F3094, F3097, L5161, F3115].
PHARMACODYNAMICS Oseltamivir is a prodrug (usually administered as phosphate) [F3094, F3097, L5161, F3115]. Once administered into the patient, it is extensively hydrolyzed by esterases located primarily in the liver to the active metabolite, the free carboxylate of oseltamivir [F3094, F3097, L5161, F3115]. In general, the specific pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that a variety of clinically significant pharmacodynamic and/or pharmacokinetic interactions may be unlikely [F3097, L5161].;
INDICATION In general, oseltamivir is indicated for the treatment of acute, uncomplicated illness due to influenza A and B infection in patients 2 weeks of age and older who have been symptomatic for no more than 48 hours [F3094]. In particular, this agent is indicated in adults and children including full-term neonates who present with symptoms typical of influenza when influenza virus is circulating in the community [F3097]. Efficacy has been demonstrated when treatment is initiated within two days of the first onset of symptoms [F3097].; ; Oseltamivir is also indicated for the prophylaxis of influenza in patients one year and older [F3094]. Specifically, post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community qualifies for such prophylactic therapy [F3097]. Oseltamivir would only be indicated for post-exposure prevention of influenza in infants less than 1 year of age during a pandemic influenza outbreak [F3097]; ;
DESCPRITION Oseltamivir phosphate is an ethyl ester prodrug requiring ester hydrolysis for conversion to the active form, oseltamivir carboxylate. Oseltamivir carboxylate is an inhibitor of influenza virus neuraminidase affecting release of viral particles. The median IC50 values of oseltamivir against influenza A/H1N1, influenza A/H3N2, and influenza B clinical isolates were 2.5 nM (range 0.93-4.16 nM, N=74), 0.96 nM (range 0.13 - 7.95 nM, N=774), and 60 nM (20-285 nM, N=256), respectively, in a neuraminidase assay with a fluorescently labeled MUNANA substrate.
DESCRIPTION Oseltamivir is an oral antiviral prodrug. Its active metabolite inhibits influenza neuraminidases and prevents new viral particles from being released from infected host cells. (GtoPdb)
MOA Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) [F3097, L5161, F3115]. The active metabolite is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface [F3097, L5161, F3115]. Viral neuraminidase enzyme activity is important both for viral entry into uninfected cells and for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body [F3097, L5161, F3115]. Oseltamivir carboxylate inhibits the neuraminidases of influenza viruses of both types A and B [F3097, L5161, F3115] Concentrations of oseltamivir carboxylate required to inhibit the enzyme activity by 50% (IC50) are in the low nanomolar range [F3097, L5161, F3115]. Oseltamivir carboxylate also inhibits influenza virus infection and replication in-vitro and inhibits influenza virus replication and pathogenicity in-vivo [F3097, L5161, F3115]. Oseltamivir carboxylate reduces shedding of both influenza A and B virus by inhibiting the release of infectious virus from infected cells [F3097, L5161, F3115].
TOXICITY Reports of overdoses with oseltamivir have been received from clinical trials and during postmarketing experience [F3094, F3097, L5161, F3115]. In the majority of cases reporting overdose, no adverse reactions were reported [F3094, F3097, L5161, F3115]. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir [F3094, F3097, L5161, F3115]. Although influenza is associated with adverse pregnancy and fetal outcomes, with a risk of major congenital malformations, including congenital heart defects, the use of oseltamivir may be considered during pregnancy if necessary and after considering the available safety and benefit information and the pathogenicity of the circulating influenza virus strain [F3094, F3097, L5161, F3115]. Based on limited published data, oseltamivir and oseltamivir carboxylate are present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant [F3094, F3097, L5161, F3115]. Exercise caution when oseltamivir phosphate for oral suspension is administered to a nursing woman [F3094, F3097, L5161, F3115]. Based on preclinical data, there is no evidence that oseltamivir has an effect on male or female fertility [F3094, F3097, L5161, F3115]. No reported clinical experience has identified differences in responses between the elderly and younger subjects [F3094, F3097, L5161, F3115]. The safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients less than 2 weeks of age have not been established [F3094, F3097, L5161, F3115]. Moreover, the safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age [F3094, F3097, L5161, F3115].
MOA Oseltamivir phosphate is a pro-drug of the active metabolite (oseltamivir carboxylate) [F3097, L5161, F3115]. The active metabolite is a potent and selective inhibitor of influenza virus neuraminidase enzymes, which are glycoproteins found on the virion surface [F3097, L5161, F3115]. Viral neuraminidase enzyme activity is important both for viral entry into uninfected cells and for the release of recently formed virus particles from infected cells, and for the further spread of the infectious virus in the body [F3097, L5161, F3115].; ; Oseltamivir carboxylate inhibits the neuraminidases of influenza viruses of both types A and B [F3097, L5161, F3115] Concentrations of oseltamivir carboxylate required to inhibit the enzyme activity by 50% (IC50) are in the low nanomolar range [F3097, L5161, F3115]. Oseltamivir carboxylate also inhibits influenza virus infection and replication in-vitro and inhibits influenza virus replication and pathogenicity in-vivo [F3097, L5161, F3115].; ; Oseltamivir carboxylate reduces shedding of both influenza A and B virus by inhibiting the release of infectious virus from infected cells [F3097, L5161, F3115].
TOXICITY Reports of overdoses with oseltamivir have been received from clinical trials and during postmarketing experience [F3094, F3097, L5161, F3115]. In the majority of cases reporting overdose, no adverse reactions were reported [F3094, F3097, L5161, F3115]. Adverse reactions reported following overdose were similar in nature to those observed with therapeutic doses of oseltamivir [F3094, F3097, L5161, F3115].; ; Although influenza is associated with adverse pregnancy and fetal outcomes, with a risk of major congenital malformations, including congenital heart defects, the use of oseltamivir may be considered during pregnancy if necessary and after considering the available safety and benefit information and the pathogenicity of the circulating influenza virus strain [F3094, F3097, L5161, F3115].; ; Based on limited published data, oseltamivir and oseltamivir carboxylate are present in human milk at low levels considered unlikely to lead to toxicity in the breastfed infant [F3094, F3097, L5161, F3115]. Exercise caution when oseltamivir phosphate for oral suspension is administered to a nursing woman [F3094, F3097, L5161, F3115].; ; Based on preclinical data, there is no evidence that oseltamivir has an effect on male or female fertility [F3094, F3097, L5161, F3115].; ; No reported clinical experience has identified differences in responses between the elderly and younger subjects [F3094, F3097, L5161, F3115].; ; The safety and efficacy of oseltamivir phosphate for the treatment of influenza in pediatric patients less than 2 weeks of age have not been established [F3094, F3097, L5161, F3115]. Moreover, the safety and efficacy of oseltamivir phosphate for prophylaxis of influenza have not been established for pediatric patients less than 1 year of age [F3094, F3097, L5161, F3115].
DESCRIPTION Viral RNA polymerase inhibitor (Tocris Bioactive Compound Library)
Cell lines
1
Organisms
8
Compound Sets
23
Axon Medchem Screening Library
3136
Cayman Chemical Bioactives
16070
CeMM library of unique drugs (CLOUD)
ChEMBL Approved Drugs
CHEMBL1200340
CHEMBL1229
ChEMBL Drugs
CHEMBL1200340
CHEMBL1229
Drug Repurposing Hub
DrugBank
DB00198
DrugBank Approved Drugs
DB00198
DrugCentral
2001
DrugCentral Approved Drugs
2001
DrugMAP
DMGO72P
DrugMAP Approved Drugs
DMGO72P
Enamine BioReference Compounds
EU-OPENSCREEN Bioactive Compound Library
EOS100668
Guide to Pharmacology
11427
MedChem Express Bioactive Compound Library
HY-17016
HY-13317
Natural product-based probes and drugs
NPC Screening Collection
ReFrame library
Selleckchem Bioactive Compound Library
oseltamivir-phosphate-Tamiflu
TargetMol Bioactive Compound Library
T1486
The Spectrum Collection
Tocris Bioactive Compound Library
7224
External IDs
68
Properties
(calculated by RDKit )
Molecular Weight
312.2
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
7
Ring Count
1
Aromatic Ring Count
0
cLogP
1.29
TPSA
90.65
Fraction CSP3
0.75
Chiral centers
3.0
Largest ring
6.0
QED
0.69
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
MOA
viral neuraminidase inhibitor
Influenza Virus inhibitor
Inhibitor
neuraminidase inhibitor
Target
neuraminidase
influenza A and B
CES1, NEU1, NEU2
Neuraminidase inhibitor
Influenza Virus
Influenza Virus,Neuraminidase
Pathway
Microbiology&virology
Anti-infection
Primary Target
Other Hydrolases
Indication
influenza A virus infection
Biosynthetic Origin
Carbohydrate (Aminoglycoside)
Therapeutic Indication
Antiviral
Therapeutic Class
Antiviral Agents
Source data