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Elexacaftor Pathway, Pharmacokinetics

PA166328401 Last updated March 2024 Caroline F. Thorn
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Drugs & chemicals
0
Genes
1/1
Conditions
10
Reactions
Elexacaftor Pathway, Pharmacokinetics pathway diagram
Elexacaftor Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
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About this pathway

Introduction

Elexacaftor is a modulator of CFTR that is designed to be used in combination with ivacaftor and tezacaftor to counteract variants that impact the proper splicing, folding, and location of CFTR to the membrane (FDA Multi-Discipline review,Elexacaftor/Tezacaftor/Ivacaftor)[Articles:38249954, 38186649, 37983082]. Ivacaftor/tezacaftor/elexacaftor is FDA and EMA indicated for the treatment of cystic fibrosis in patients 6 years and older who have at least one F508del mutation.

Pharmacokinetics

Metabolism

Elexacaftor is metabolized in the liver by CYP3A4 and CYP3A5 and excreted primarily in bile (FDA Multi-Discipline review,Elexacaftor/Tezacaftor/Ivacaftor)[Articles:36036885, 37259485]. The major metabolite is elexacaftor metabolite m23, which has about one third activity towards CFTR compared to that of the parent drug (FDA Multi-Discipline review,Elexacaftor/Tezacaftor/Ivacaftor).

Transport

No transporters are reported where elexacaftor is a substrate however in vitro it is an inhibitor of SLCO1B1 and SLCO1B3 [Article:37259485] (FDA Multi-Discipline review,Elexacaftor/Tezacaftor/Ivacaftor).

Reactions & interactions (10)

  • Biochemical Reaction
    elexacaftor elexacaftor metabolite m23
  • Catalysis
    CYP3A5 Biochemical Reaction
  • Catalysis
    CYP3A4 Biochemical Reaction
  • Inhibition
    elexacaftor SLCO1B1
  • Inhibition
    elexacaftor metabolite m23 SLCO1B1
  • Inhibition
    elexacaftor metabolite m23 SLCO1B3
  • Inhibition
    elexacaftor SLCO1B3
  • Leads To
    elexacaftor metabolite m23 Ivacaftor pathway, pharmacokinetics/pharmacodynamics
  • Leads To
    Ivacaftor pathway, pharmacokinetics/pharmacodynamics Cystic Fibrosis
  • Leads To
    elexacaftor Ivacaftor pathway, pharmacokinetics/pharmacodynamics

Edit history (2)

  • 2024-02-28 Create
  • 2024-03-14 Update Added related pathways
Elexacaftor Pathway, Pharmacokinetics pathway diagram (enlarged)