Telotristat ethyl

Telotristat ethyl

Clinical data
Trade names	Xermelo
Other names	LX1032, LX1606
AHFS/Drugs.com	Monograph
MedlinePlus	a617029
License data	US DailyMed: Telotristat_ethyl
Pregnancy category	AU: B3
Routes of administration	By mouth (tablets)
ATC code	A16AX15 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only EU: Rx-only
Pharmacokinetic data
Protein binding	>99% (both telotristat ethyl and telotristat)
Metabolism	Hydrolysis via carboxylesterases
Metabolites	Telotristat
Elimination half-life	0.6 hours (telotristat ethyl), 5 hours (telotristat)
Excretion	Feces (92.8%), urine (less than 0.4%)
Identifiers
IUPAC name [(S)-Ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate]
CAS Number	1033805-22-9
PubChem CID	25181577
DrugBank	DB12095
ChemSpider	28189674
UNII	8G388563M7
KEGG	D09974 as etiprate: D09975
ChEMBL	ChEMBL2105695
Chemical and physical data
Formula	C27H26ClF3N6O3
Molar mass	574.99 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCOC(=O)C(CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)OC(C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)N
InChI InChI=1S/C27H26ClF3N6O3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35)/t20-,24+/m0/s1 Key:MDSQOJYHHZBZKA-GBXCKJPGSA-N

Telotristat ethyl (USAN, brand name Xermelo) is a prodrug of telotristat, which is an inhibitor of tryptophan hydroxylase. It is formulated as telotristat etiprate — a hippurate salt of telotristat ethyl.

On February 28, 2017, the U.S. Food and Drug Administration (FDA) approved telotristat ethyl in combination with somatostatin analog (SSA) therapy for the treatment of adults with diarrhea associated with carcinoid syndrome that SSA therapy alone has inadequately controlled. Telotristat ethyl was approved for use in the European Union in September 2017.

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Pharmacology

Telotristat is an inhibitor of tryptophan hydroxylase, which mediates the rate-limiting step in serotonin biosynthesis.

Action of telotristat on tryptophan hydroxylase

Adverse effects

Common adverse effects noted in clinical trials include nausea, headache, elevated liver enzymes, depression, accumulation of fluid causing swelling (peripheral edema), flatulence, decreased appetite, and fever. Constipation is also common, and may be serious or life-threatening (especially in overdose).

Formulations

It is marketed by Lexicon Pharmaceuticals (as telotristat etiprate). 328 mg telotristat etiprate is equivalent to 250 mg telotristate ethyl.

Telotristat etiprate

Further reading

• Kulke MH, O'Dorisio T, Phan A, Bergsland E, Law L, Banks P, et al. (October 2014). "Telotristat etiprate, a novel serotonin synthesis inhibitor, in patients with carcinoid syndrome and diarrhea not adequately controlled by octreotide". Endocrine-Related Cancer. 21 (5): 705–14. doi:10.1530/ERC-14-0173. PMC 4295770. PMID 25012985.

External links

• "Telotristat ethyl". Drug Information Portal. U.S. National Library of Medicine.
• "Telotristat etiprate". Drug Information Portal. U.S. National Library of Medicine.