General
Preferred name
TRICLABENDAZOLE
Synonyms
CPD000466357 ()
CGA89317 ()
CGA-89317,tcbz ()
Fasinex ()
Egaten tm ()
NVP-EGA230 ()
Egaten ()
NSC-759250 ()
EGA230B ()
Triclabendazole-13C-d3 ()
P&D ID
PD000272
CAS
68786-66-3
2938916-53-9
Tags
natural product
drug
available
Approved by
FDA
First approval
2019
1990
Drug Status
investigational
approved
Drug indication
Helminth infection
Max Phase
Phase 4
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)
INDICATION
This drug is indicated for the treatment of fascioliasis in patients 6 years of age and older [FDA label], [L5452].
ROE
No data regarding excretion is available in humans. In animals, triclabendazole is primarily excreted by the biliary tract in the feces (90%), together with the sulfoxide and sulfone metabolite. Less than 10% of an oral dose is found excreted in the urine [FDA label].
HALF-LIFE
The plasma elimination half-life (t1/2) of triclabendazole, the sulfoxide and sulfone metabolites in human is about 8, 14, and 11 hours, respectively.[FDA label]
PHARMACODYNAMICS
Triclabendazole and its metabolites are active against both the immature and mature worms of _Fasciola hepatica_ and _Fasciola gigantica_ helminths [FDA label]. **Effect on QT interval** This drug may prolong the cardiac QT interval. Monitor ECG in patients with a history of QT prolongation or who are taking medications known to prolong the QT interval. Triclabendazole exposure-response relationships and the time course of pharmacodynamics response are not known at this time [FDA label].
HALF-LIFE
The plasma elimination half-life (t1/2) of triclabendazole, the sulfoxide and sulfone metabolites in human is about 8, 14, and 11 hours, respectively [FDA label].
MOA
Triclabendazole is an anthelmintic agent against _Fasciola_ species [FDA label]. The mechanism of action against Fasciola species is not fully understood at this time. In vitro studies and animal studies suggest that triclabendazole and its active metabolites (_sulfoxide_ and _sulfone_) are absorbed by the outer body covering of the immature and mature worms, causing a reduction in the resting membrane potential, the inhibition of tubulin function as well as protein and enzyme synthesis necessary for survival. These metabolic disturbances lead to an inhibition of motility, disruption of the worm outer surface, in addition to the inhibition of spermatogenesis and egg/embryonic cells [FDA label]. **A note on resistance** In vitro studies, in vivo studies, as well as case reports suggest a possibility for the development of resistance to triclabendazole. The mechanism of resistance may be multifactorial and include changes in drug uptake/efflux mechanisms, target molecules, and changes in drug metabolism. The clinical significance of triclabendazole resistance in humans is not yet elucidated [FDA label].
TOXICITY
**Oral LD50 (rat)**: >8 gm/kg; Oral LD50 (mouse): >8 gm/kg [MSDS]. **A note on the use in pregnancy** There are no available data on triclabendazole use in pregnant women to calculate a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Reproductive studies in animals (rat and rabbits) have not demonstrated an increased risk of increased fetal abnormalities with exposure to triclabendazole during the organogenesis period at doses which were about 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg [FDA label]. **Carcinogenesis/Mutagenesis** No genotoxic risk was noted for triclabendazole tested in 6 genotoxicity in vitro and in vivo assays. **Impairment of Fertility** No drug-related effects on reproductive performance, mating ratios or indices of fertility have been observed in a 2-generation reproductive and developmental toxicity study in rats [FDA label]. **A note on use in breastfeeding** There are no human findings on the presence of triclabendazole in milk, the effects on the breastfed infant, or the effects on milk production. The results of animal studies indicate that triclabendazole is found in goat milk when given as a single dose to one lactating animal. When a drug is found in animal milk, it is likely that the drug will also be found in human milk [FDA label].
METABOLISM
Based on in vitro studies, triclabendazole is mainly metabolized by CYP1A2 enzyme (approximately 64%) into its active _sulfoxide_ metabolite and to a lesser extent by CYP2C9, CYP2C19, CYP2D6, CYP3A, and FMO (flavin containing monooxygenase). This sulfoxide metabolite is further metabolized mainly by CYP2C9 to the active sulfone metabolite, and to a smaller extent by CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, and CYP3A4, _in vitro_ [FDA label].
PHARMACODYNAMICS
Triclabendazole and its metabolites are active against both the immature and mature worms of _Fasciola hepatica_ and; _Fasciola gigantica_ helminths.[FDA label]; ; **Effect on QT interval**; ; This drug may prolong the cardiac QT interval. Monitor ECG in patients with a history of QT prolongation or who are taking medications known to prolong the QT interval.[FDA label] ; ; Triclabendazole exposure-response relationships and the time course of pharmacodynamics response are not known at this time.[FDA label]
MOA
Triclabendazole is an anthelmintic agent against _Fasciola_ species.[FDA label]; ; The mechanism of action against Fasciola species is not fully understood at this time. In vitro studies and animal studies suggest that triclabendazole and its active metabolites (_sulfoxide_ and _sulfone_) are absorbed by the outer body covering of the immature and mature worms, causing a reduction in the resting membrane potential, the inhibition of tubulin function as well as protein and enzyme synthesis necessary for survival. These metabolic disturbances lead to an inhibition of motility, disruption of the worm outer surface, in addition to the inhibition of spermatogenesis and egg/embryonic cells.[FDA label]; ; **A note on resistance**; ; In vitro studies, in vivo studies, as well as case reports suggest a possibility for the development of resistance to triclabendazole.; The mechanism of resistance may be multifactorial and include changes in drug uptake/efflux mechanisms, target molecules, and changes in drug metabolism. The clinical significance of triclabendazole resistance in humans is not yet elucidated.[FDA label]
INDICATION
This drug is indicated for the treatment of fascioliasis in patients aged 6 years old and above.[FDA label,L5452]
ROE
No data regarding excretion is available in humans. In animals, triclabendazole is primarily excreted by the biliary tract in the feces (90%), together with the sulfoxide and sulfone metabolite. Less than 10% of an oral dose is found excreted in the urine.[FDA label]
METABOLISM
Based on in vitro studies, triclabendazole is mainly metabolized by CYP1A2 enzyme (approximately 64%) into its active _sulfoxide_ metabolite and to a lesser extent by CYP2C9, CYP2C19, CYP2D6, CYP3A, and FMO (flavin containing monooxygenase). This sulfoxide metabolite is further metabolized mainly by CYP2C9 to the active sulfone metabolite, and to a smaller extent by CYP1A1, CYP1A2, CYP1B1, CYP2C19, CYP2D6, and CYP3A4, _in vitro_.[FDA label]
ABSORPTION
After a single oral dose of 10 mg/kg triclabendazole with a 560-kcal meal to patients diagnosed with fascioliasis, mean peak plasma concentrations (Cmax) for triclabendazole, the sulfoxide, and sulfone metabolites were 1.16, 38.6, and 2.29 μmol/L, respectively. The area under the curve (AUC) for triclabendazole, the sulfoxide and sulfone metabolites were 5.72, 386, and 30.5 μmolâh/L, respectively [FDA label]. After the oral administration of a single dose of triclabendazole at 10 mg/kg with a 560 calorie meal to patients with fascioliasis, the median Tmax for the parent compound as well as the active sulfoxide metabolite was 3 to 4 hours [FDA label]. **Effect of Food** Cmax and AUC of triclabendazole and sulfoxide metabolite increased about 2-3 times when triclabendazole was administered as a single dose at 10 mg/kg with a meal containing approximately 560 calories. Additionally, the sulfoxide metabolite Tmax increased from 2 hours in fasting subjects to 4 hours in fed subjects [FDA label].
TOXICITY
**Oral LD50 (rat)**: >8 gm/kg; Oral LD50 (mouse): >8 gm/kg[MSDS]; ; **A note on the use in pregnancy**; ; There are no available data on triclabendazole use in pregnant women to calculate a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Reproductive studies in animals (rat and rabbits) have not demonstrated an increased risk of increased fetal abnormalities with exposure to triclabendazole during the organogenesis period at doses which were about 0.3 to 1.6 times the maximum recommended human dose (MRHD) of 20 mg/kg.[FDA label]; ; **Carcinogenesis/Mutagenesis**; ; No genotoxic risk was noted for triclabendazole tested in 6 genotoxicity in vitro and in vivo assays.[FDA label[; ; **Impairment of Fertility**; ; No drug-related effects on reproductive performance, mating ratios or indices of fertility have been observed in a 2-generation reproductive and developmental toxicity study in rats.[FDA label]; ; **A note on use in breastfeeding**; ; There are no human findings on the presence of triclabendazole in milk, the effects on a nursing infant, or the effects on maternal milk production. The results of animal studies indicate that triclabendazole is found in goat milk when given as a single dose to a lactating female goat. When a drug is found to be present in animal milk, the likelihood that it will be found in human milk is high. Excercise caution if this drug is administered during nursing.[FDA label]
ABSORPTION
After a single oral dose of 10 mg/kg triclabendazole with a 560-kcal meal to patients diagnosed with fascioliasis, mean peak plasma concentrations (Cmax) for triclabendazole, the sulfoxide, and sulfone metabolites were 1.16, 38.6, and 2.29 μmol/L, respectively. The area under the curve (AUC) for triclabendazole, the sulfoxide and sulfone metabolites were 5.72, 386, and 30.5 μmolâh/L, respectively.[FDA label]; ; After the oral administration of a single dose of triclabendazole at 10 mg/kg with a 560 calorie meal to patients with fascioliasis, the median Tmax for the parent compound as well as the active sulfoxide metabolite was 3 to 4 hours.[FDA label]; ; **Effect of Food**; Cmax and AUC of triclabendazole and sulfoxide metabolite increased about 2-3 times when triclabendazole was administered as a single dose at 10 mg/kg with a meal containing approximately 560 calories. Additionally, the sulfoxide metabolite Tmax increased from 2 hours in fasting subjects to 4 hours in fed subjects [FDA label].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
0
Organisms
2
Compound Sets
20
Bioprocess diversity set
ChEMBL Approved Drugs
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DrugBank Approved Drugs
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The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
38
Molecular Weight
357.95
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
3
Ring Count
3
Aromatic Ring Count
3
cLogP
6.04
TPSA
37.91
Fraction CSP3
0.07
Chiral centers
0.0
Largest ring
6.0
QED
0.58
Structural alerts
2
aggregator (Aggregator Advisor)
Aggregators
aggregator (ZINC)
Aggregators
Related compounds
Custom attributes
(extracted from source data)
Biological process
Cell polarity & morphogenesis
Pathway
Cytoskeletal Signaling
Anti-infection
Apoptosis
Cell Cycle/DNA Damage
Epigenetics
Immunology/Inflammation
Target
Tubulin
DNMT1
Bcl-2 Family
Caspase
Parasite
PARP
Pyroptosis
Microtubule Associated
Indication
tapeworm
MOA
microtubule inhibitor
Source data
