Velpatasvir

Velpatasvir
Clinical data
Trade namesEpclusa, Sofosvel, Velpanat (all in combination with sofosbuvir)
Routes of
administration		Oral (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding>99.5%
MetabolismLiver (CYP2B6, 2C8, 3A4)
Elimination half-life15 hours
ExcretionFeces (94%), urine (0.4%)[1]
Identifiers
  • Methyl {(2S)-1-[(2S,5S)-2-(9-{2-[(2S,4S)-1-{(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl}-4-(methoxymethyl)-2-pyrrolidinyl]-1H-imidazol-4-yl}-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-2-yl)-5-methyl-1-pyrrolidinyl]-3-methyl-1-oxo-2-butanyl}carbamate
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC49H54N8O8
Molar mass883.019 g·mol−1
3D model (JSmol)
  • COC[C@H]1C[C@@H](c2ncc(-c3ccc4c(c3)COc3cc5c(ccc6[nH]c([C@@H]7CC[C@H](C)N7C(=O)[C@@H](NC(=O)OC)C(C)C)nc65)cc3-4)[nH]2)N(C(=O)[C@H](NC(=O)OC)c2ccccc2)C1
  • InChI=1S/C49H54N8O8/c1-26(2)41(54-48(60)63-5)47(59)57-27(3)12-17-38(57)45-51-36-16-14-30-20-35-33-15-13-31(19-32(33)25-65-40(35)21-34(30)43(36)53-45)37-22-50-44(52-37)39-18-28(24-62-4)23-56(39)46(58)42(55-49(61)64-6)29-10-8-7-9-11-29/h7-11,13-16,19-22,26-28,38-39,41-42H,12,17-18,23-25H2,1-6H3,(H,50,52)(H,51,53)(H,54,60)(H,55,61)/t27-,28-,38-,39-,41-,42+/m0/s1
  • Key:FHCUMDQMBHQXKK-CDIODLITSA-N

Velpatasvir is an NS5A inhibitor (by Gilead) which is used together with sofosbuvir in the treatment of hepatitis C infection of all six major genotypes.[2][3]

Side effects

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Further information: Velpatasvir/sofosbuvir § Side effects

Side effects in studies occurred with similar frequencies as in people treated with placebo.[4]

Interactions

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Velpatasvir is both an inhibitor and a substrate of the transporter proteins P-glycoprotein (Pgp), ABCG2, OATP1B1 and OATP1B3. It is partly degraded by the liver enzymes CYP2B6, CYP2C8 and CYP3A4. Substances that are transported or inactivated by these proteins, or interfere with them, can interact with velpatasvir. In studies, this has been found for the HIV combination efavirenz/emtricitabine/tenofovir, which reduces the area under the curve (AUC) of velpatasvir by about 50%, and the CYP3A4 and Pgp inducer rifampicin, which reduces its AUC by about 80%, rendering it likely ineffective. Digoxin is eliminated by Pgp; its AUC is increased by about 30% in combination with velpatasvir and sofosbuvir (although it is not clear which of the two is responsible for this effect).[4]

Substances that reduce gastric acid, such as antacids, H2 blockers, and proton pump inhibitors, reduce velpatasvir AUC by 20–40%.[4]

Pharmacology

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Mechanism of action

[edit]
Further information: Discovery and development of NS5A inhibitors § Mechanism of action

The substance blocks NS5A, a protein necessary for hepatitis C virus replication and assembly.[4]

Pharmacokinetics

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Velpatasvir reaches highest blood plasma levels three hours after oral intake together with sofosbuvir. Plasma protein binding is over 99.5%. It is slowly metabolised by the liver enzymes CYP2B6, CYP2C8 and CYP3A4. While monohydroxylated and demethylated metabolites have been identified in human blood plasma and faeces, over 98% of the circulating substance is velpatasvir itself.[4] 94% are excreted via the faeces, and only 0.4% via the urine.[1] Biological half-life is about 15 hours.[4]

See also

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References

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  1. ^ a b "Epclusa (sofosbuvir and velpatasvir) Tablets, for Oral Use. Full Prescribing Information" (PDF). Gilead Sciences, Inc. Foster City, CA 94404. Retrieved 1 August 2016.
  2. ^ "FDA Approves Epclusa". Drugs.com.
  3. ^ Heo YA, Deeks ED (April 2018). "Sofosbuvir/Velpatasvir/Voxilaprevir: A Review in Chronic Hepatitis C". Drugs. 78 (5): 577–587. doi:10.1007/s40265-018-0895-5. PMID 29546556.
  4. ^ a b c d e f Haberfeld H, ed. (2016). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Epclusa 400 mg/100 mg Filmtabletten.
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