General
Preferred name
TRAVOPROST
Synonyms
Fluprostenol isopropyl ester ()
AL6221 ()
Flu-Ipr ()
travoprost 0.004%, Alcon ()
Travoprostum ()
Izba ()
NSC-760366 ()
Travatan ()
Travatan Z ()
Otx-tp ()
AL-6221 ()
(+)-Fluprostenol isopropyl ester ()
Fluprostenol isopropyl ester-d4 ()
P&D ID
PD010123
CAS
157283-68-6
Tags
available
prodrug
drug
Approved by
FDA
EMA
First approval
2001
Drug indication
Open-angle glaucoma
Drug Status
approved
Max Phase
4.0
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The terminal elimination half-life of travoprost free acid is determined to be approximately 45 minutes, although studies demonstrated half-life values that ranged from 17 to 86 minutes [F3061, F3064].
ABSORPTION
Travoprost is systemically absorbed through the cornea [F3061, F3064, L5146]. In humans, peak plasma concentrations of travoprost free acid were low (25 pg/mL or less) and occurred within 30 minutes following topical ocular administration of one drop of 0.004% travoprost ophthalmic solution [F3061, F3064, L5146].
ROE
Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid [F3061, F3064, L5146]. Moreover, elimination from plasma is rapid, resulting in concentrations below the limit of quantitation (< 10 pg/mL) by one hour [F3061, F3064, L5146]. Furthermore, in rats, 95% of a subcutaneous radiolabeled dose was eliminated within 24 hours [F3061, F3064]. The major route of elimination was via the bile (61%) with the remainder excreted by the kidneys [F3061, F3064].
PHARMACODYNAMICS
Travoprost, an isopropyl ester prodrug, is a synthetic prostaglandin F2 alpha analog that is rapidly hydrolyzed by esterases in the cornea to its biologically active free acid [FDA Label]. The travoprost free acid is potent and highly selective for the FP prostanoid receptor [FDA Label].
MOA
Travoprost, a prostaglandin F2α analogue, is a highly selective full agonist which has a high affinity for the prostaglandin FP receptor, and facilitates reductions in intraocular pressure by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways [F3061, F3064, L5146]. Reduction of the intraocular pressure in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose [F3061, F3064, L5146].
INDICATION
Travoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension [F3061, F3064, L5146]. Travoprost is also currently indicated for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma [L5146].
METABOLISM
Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid [F3061, F3064]. Systemically, travoprost free acid is rapidly and extensively metabolized in the kidney, liver, and lung to inactive metabolites via beta-oxidation of the α(carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13,14 double bond [F3061, F3064].
INDICATION
Travoprost ophthalmic solution is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension [F3061, F3064, L5146].; ; Travoprost is also currently indicated for the decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma [L5146].
ROE
Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid [F3061, F3064, L5146]. Moreover, elimination from plasma is rapid, resulting in concentrations below the limit of quantitation (< 10 pg/mL) by one hour [F3061, F3064, L5146].; ; Furthermore, in rats, 95% of a subcutaneous radiolabeled dose was eliminated within 24 hours [F3061, F3064]. The major route of elimination was via the bile (61%) with the remainder excreted by the kidneys [F3061, F3064].
DESCRIPTION
Travoprost is an analogue of prostaglindin F2α (). The drug itself is a prodrug that is hydrolysed in vivo to an active free acid form.
(GtoPdb)
TOXICITY
No cases of overdose have been reported for travoprost [L5146]. A topical overdose is not likely to occur or to be associated with toxicity [L5146]. A topical overdose of travoprost may be flushed from the eye(s) with lukewarm water [L5146]. Treatment of a suspected oral ingestion is symptomatic and supportive [L5146]. Travoprost has harmful pharmacological effects on pregnancy and/or the fetus/new-born child. Travoprost should not be used during pregnancy unless clearly necessary [L5146]. The medication subsequently must not be used in women of childbearing age/potential unless adequate contraceptive measures are in place [L5146]. It is unknown whether travoprost from the eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk [F3061, F3064, L5146]. The use of travoprost by breast-feeding mothers is not recommended [L5146]. There are no data on the effects of TRAVATAN on human fertility [F3061, F3064, L5146]. Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose [L5146]. Use in patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use [F3061, F3064]. No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients [F3061, F3064]. Travoprost has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min) [L514. No dosage adjustment is necessary for these patients [L5146].
TOXICITY
No cases of overdose have been reported for travoprost [L5146]. A topical overdose is not likely to occur or to be associated with toxicity [L5146]. A topical overdose of travoprost may be flushed from the eye(s) with lukewarm water [L5146]. Treatment of a suspected oral ingestion is symptomatic and supportive [L5146].; ; Travoprost has harmful pharmacological effects on pregnancy and/or the fetus/new-born child. Travoprost should not be used during pregnancy unless clearly necessary [L5146]. The medication subsequently must not be used in women of childbearing age/potential unless adequate contraceptive measures are in place [L5146].; ; It is unknown whether travoprost from the eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk [F3061, F3064, L5146]. The use of travoprost by breast-feeding mothers is not recommended [L5146].; ; There are no data on the effects of TRAVATAN on human fertility [F3061, F3064, L5146]. Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose [L5146].; ; Use in patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use [F3061, F3064].; ; No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients [F3061, F3064].; ; Travoprost has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min) [L514. No dosage adjustment is necessary for these patients [L5146].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
18
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
Mcule NIBR MoA Box Subset
MedChem Express Bioactive Compound Library
NCATS Inxight Approved Drugs
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
Selleckchem Bioactive Compound Library
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
38
Molecular Weight
500.24
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
3
Rotatable Bonds
12
Ring Count
2
Aromatic Ring Count
1
cLogP
4.43
TPSA
96.22
Fraction CSP3
0.58
Chiral centers
5.0
Largest ring
6.0
QED
0.22
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Member status
virtual
MOA
Prostanoid FP Agonists
prostanoid receptor agonist
Indication
ocular hypertension, glaucoma
Target
PTGFR
Prostaglandin Receptor
Therapeutic Class
Ophthalmologicals
Pathway
GPCR/G protein
Source data
