Grazoprevir

Source: Wikipedia, the free encyclopedia.
Grazoprevir
Clinical data
Trade namesZepatier (combination with elbasvir)
Other namesMK-5172
License data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding98.8%
MetabolismCYP3A4
Elimination half-life31 hours
Excretion>90% via faeces, <1% via urine
Identifiers
  • (1R,18R,20R,24S,27S)-N-{(1R,2S)-1-[(Cyclopropylsulfonyl)carbamoyl]-2-vinylcyclopropyl}-7-methoxy-24-(2-methyl-2-propanyl)-22,25-dioxo-2,21-dioxa-4,11,23,26-tetraazapentacyclo[24.2.1.03,12.05,10.0 18,20]nonacosa-3,5,7,9,11-pentaene-27-carboxamide
JSmol
)
  • O=C1C(C(C)(C)C)NC(=O)OC3CC3CCCCCc2nc4ccc(OC)cc4nc2OC(C6)CN1C6C(=O)NC5(CC5C=C)C(=O)NS(=O)(=O)C7CC7
  • InChI=1S/C38H50N6O9S/c1-6-22-19-38(22,35(47)43-54(49,50)25-13-14-25)42-32(45)29-18-24-20-44(29)34(46)31(37(2,3)4)41-36(48)53-30-16-21(30)10-8-7-9-11-27-33(52-24)40-28-17-23(51-5)12-15-26(28)39-27/h6,12,15,17,21-22,24-25,29-31H,1,7-11,13-14,16,18-20H2,2-5H3,(H,41,48)(H,42,45)(H,43,47)/t21-,22-,24-,29+,30-,31-,38-/m1/s1
  • Key:OBMNJSNZOWALQB-NCQNOWPTSA-N

Grazoprevir is a drug

Zepatier, either with or without ribavirin.[2]

Grazoprevir is a second generation

4A protease targets.[3] It has good activity against a range of HCV genotype variants, including some that are resistant to most currently used antiviral medications.[4][5]

Side effects

Main article: Elbasvir/grazoprevir § Side effects

Side effects have only been assessed in the combination with

reduced appetite, and headache. Low red blood cell count has occurred when co-administered with ribavirin in some cases.[6][7] The most important risks are alanine transaminase elevation, hyperbilirubinemia, drug resistance development and drug interactions.[8]

Interactions

Grazoprevir is transported by the

SLCO1B3. Drugs that inhibit this proteins, such as rifampicin, ciclosporin, and a number of AIDS medications (atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cobicistat
), can cause a significant increase in grazoprevir blood plasma levels. The substance is degraded by the liver enzyme
St. John's wort, can lead to ineffectively low plasma levels of grazoprevir. Combination with CYP3A4 inhibitors may increase plasma levels.[7][9]

Pharmacology

Mechanism of action

Grazoprevir blocks

NS4A, a cofactor of NS3.[7]

Pharmacokinetics

Grazoprevir reaches peak plasma concentrations two hours after oral intake together with elbasvir (variation between patients: 30 minutes to three hours). In hepatitis C patients, steady state concentrations are found after about six days.

faeces, and less than 1% via the urine.[7]

References

  1. ^ "FDA approves Zepatier for treatment of chronic hepatitis C genotypes 1 and 4". Food and Drug Administration. 2018-11-03.
  2. PMID 25467591
    .
  3. PMID 24900473
    .
  4. PMID 22615282
    .
  5. S2CID 207477059
    .
  6. ^ "ZEPATIER (elbasvir and grazoprevir) Tablets, for Oral Use. Full Prescribing Information" (PDF). Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. Retrieved 31 January 2016.
  7. ^ a b c d Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
  8. ^ "European Public Assessment Report" (PDF). European Medicines Agency. Retrieved 16 December 2017.
  9. ^ FDA Professional Drug Information on Zepatier.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Grazoprevir&oldid=1158157063"