Choosing a pharmacogenomic strategy for targeted therapy of cystic fibrosis: the story of one patient
https://doi.org/10.37489/2588-0527-2025-2-40-45
EDN: YZOOUU
Abstract
Relevance. The study of pharmacokinetic and pharmacodynamic drug interactions involving components of targeted medications demonstrates the lack of available data and the significant need for research aimed at describing the likelihood, extent, and clinical impact of proposed drug interactions for individual patients and for the population of patients with cystic fibrosis.
Objective. To describe a clinical case of a patient with cystic fibrosis F508del in the CFTR gene in combination with PIDS (Common Variable Immune Deficiency) a carrier of the potentially "problematic" CYP3A5 *3/*3 and SLCO1B1 *1/*5 genotypes for liver metabolism, with an assessment of the safety of the targeted therapy for cystic fibrosis.
Materials and methods. For genetic analysis, the isolated DNA was examined using the iPLEX Pro PGx panel (Agena Bioscience) in the "VeriDose® Core Panel" modification, the patient revealed: P-glycoprotein (P-gp) gene ABCB1 (rs1045642) G/G, APOE E2/E3, CYP1A2*1A/*1F, CYP2B6*1/*1, CYP2C19*1/*1 , CYP3A4*1/*1 , CYP3A5*3/*3 , PNPLA5 (RS5764010) C/C and SLCO1B1*1/*5 .
Results. The patient's biochemical abnormalities were clarified during the selection of a drug for targeted therapy of cystic fibrosis, as well as during the use and switching of targets. Clinically insignificant abnormalities in biochemical liver function parameters were not accompanied by clinical symptoms.
Conclusion. Modern pharmacogenetic testing capabilities have made it possible to identify a potentially "problematic" combination of CYP3A *3/*3 and SLCO1B1 *1/*5 genotypes in a patient, which is associated with changes in drug metabolism in the liver. Therefore, the use of pharmacogenetic testing in patients with genetic diseases opens up opportunities for personalization and improvement of pharmacotherapy safety, allowing for the prevention or delay of organ dysfunction to enhance.
Keywords
cystic fibrosis,
ivacaftor,
tezacaftor,
elexacaftor,
drug interactions,
pharmacokinetics,
CFTR modulator
Supporting agencies: The authors express their gratitude to the Sunflower Charitable Foundation for conducting the genetic research
About the Authors
A. V. Vlasova
Morozov Children’s Clinical Hospital of the Moscow Healthcare; Russian Medical Academy of Continuous Professional Education
Russian Federation
Competing Interests:
Russian Federation
Anna V. Vlasova — PhD, Dr. Sci. (Med.), Associate Professor, Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Russian Medical Academy of Continuous Professional Education; Head of the Department of Clinical Pharmacology Morozov Children’s Clinical Hospital of the Moscow Healthcare.
Moscow
Competing Interests:
The authors declare no conflict of interest
E. E. Yakushina
Morozov Children’s Clinical Hospital of the Moscow Healthcare
Russian Federation
Competing Interests:
Russian Federation
Elena E. Yakushina — Pediatrician, Morozov Children’s Clinical Hospital of the Moscow Healthcare
Moscow
Competing Interests:
The authors declare no conflict of interest
I. R. Gaziev
Morozov Children’s Clinical Hospital of the Moscow Healthcare
Russian Federation
Competing Interests:
Russian Federation
Ivan R. Gaziev — doctor of clinical laboratory diagnostics at the molecular biology laboratory, Morozov Children’s Clinical Hospital of the Moscow Healthcare.
Moscow
Competing Interests:
The authors declare no conflict of interest
O. I. Simonova
Morozov Children’s Clinical Hospital of the Moscow Healthcare; National Medical Research Center for Children's Health
Russian Federation
Competing Interests:
Russian Federation
Olga I. Simonova — PhD, Dr. Sci. (Med.), Pulmonologist, Head of the Cystic Fibrosis Center, Morozov Children’s Clinical Hospital of the Moscow Healthcare.
Moscow
Competing Interests:
The authors declare no conflict of interest
U. V. Lukash
Morozov Children’s Clinical Hospital of the Moscow Healthcare; Russian Medical Academy of Continuous Professional Education
Russian Federation
Competing Interests:
Russian Federation
Ulyana V. Lukash — Pdoctor-clinical pharmacologist, Morozov Children’s Clinical Hospital of the Moscow Healthcare; Postgraduate Student of the Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Russian Medical Academy of Continuous Professional Education.
Moscow
Competing Interests:
The authors declare no conflict of interest
D. A. Sychev
Russian Scientific Center of Surgery named after Academician B. V. Petrovsky; Russian Medical Academy of Continuous Professional Education
Russian Federation
Competing Interests:
Russian Federation
Dmitry A. Sychev — PhD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences, Academician of the Russian Academy of Sciences, Scientific Director of the World-Class Genomic Research Center “Center for Predictive Genetics, Pharmacogenetics and Personalized Therapy” of the B.V. Petrovsky Russian Scientific Center of Surgery; Head of the Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Russian Medical Academy of Continuous Professional Education.
Moscow
Competing Interests:
The authors declare no conflict of interest
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Review
For citations:
Vlasova A.V., Yakushina E.E., Gaziev I.R., Simonova O.I., Lukash U.V., Sychev D.A. Choosing a pharmacogenomic strategy for targeted therapy of cystic fibrosis: the story of one patient. Pharmacogenetics and Pharmacogenomics. 2025;(2):40-45. (In Russ.) https://doi.org/10.37489/2588-0527-2025-2-40-45. EDN: YZOOUU
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