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PharmGKB · ClinPGx

Tezacaftor Pathway, Pharmacokinetics

PA166328181 Last updated March 2024 Caroline F. Thorn
1/4
Drugs & chemicals
0
Genes
1/1
Conditions
15
Reactions
Tezacaftor Pathway, Pharmacokinetics pathway diagram
Tezacaftor Pathway, Pharmacokinetics — pathway diagram from PharmGKB / ClinPGx
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About this pathway

Introduction

Tezacaftor is a modulator of CFTR that is designed to be used together with ivacaftor to counteract variants that impact the proper splicing, folding, and location of CFTR to the membrane (FDA Multi-Discipline review,Tezacaftor/Ivacaftor).

Pharmacokinetics

Metabolism

Tezacaftor is metabolized extensively and excreted in feces [Article:37259485]. In vitro, tezacaftor is metabolized mainly by CYP3A4 and CYP3A5. There are three main metabolites found in plasma tezacaftor metabolite m1, tezacaftor metabolite m2, and tezacaftor metabolite m5. Tezacaftor metabolite m1 is considered pharmacologically active and similar to the parent drug whereas m2 is much less pharmacologically active than tezacaftor or m1, and m5 is not considered pharmacologically active (FDA Multi-Discipline review,Tezacaftor/Ivacaftor). Another minor circulating metabolite, m3, is formed by direct glucuronidation of tezacaftor but structures were not available in any database and it is not shown here (FDA Multi-Discipline review,Tezacaftor/Ivacaftor).

Transport

In vitro evidence shows that tezacaftor is a substrate for the hepatic uptake transporter SLCO1B1 [Article:37259485]. Efflux occurs in vitro via the Pgp transporter encoded by ABCB1 [Article:37259485]. The FDA Multi-Discipline review,Tezacaftor/Ivacaftor also mentions ABCG2 (BCRP) as a possible export transporter however no peer reviewed evidence documents this.

Reactions & interactions (15)

  • Biochemical Reaction
    tezacaftor → tezacaftor metabolite m2
  • Biochemical Reaction
    tezacaftor → tezacaftor metabolite m5
  • Biochemical Reaction
    tezacaftor → tezacaftor metabolite m1
  • Catalysis
    SLCO1B1 → Transport
  • Catalysis
    ABCB1 → Transport
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Catalysis
    CYP3A5 → Biochemical Reaction
  • Catalysis
    CYP3A4 → Biochemical Reaction
  • Leads To
    Ivacaftor pathway, pharmacokinetics/pharmacodynamics → Cystic Fibrosis
  • Leads To
    tezacaftor → Ivacaftor pathway, pharmacokinetics/pharmacodynamics
  • Transport
    tezacaftor → tezacaftor
  • Transport
    tezacaftor → tezacaftor

Edit history (2)

  • 2024-02-26 Create
  • 2024-03-14 Update Added related pathways
Tezacaftor Pathway, Pharmacokinetics pathway diagram (enlarged)