Cargando…

Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis

(1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransf...

Descripción completa

Detalles Bibliográficos
Autores principales: Zyryanov, Sergey K., Ushkalova, Elena A., Kondratyeva, Elena I., Butranova, Olga I., Kondakova, Yulia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139162/
https://www.ncbi.nlm.nih.gov/pubmed/35625789
http://dx.doi.org/10.3390/biomedicines10051050
_version_ 1784714794705616896
author Zyryanov, Sergey K.
Ushkalova, Elena A.
Kondratyeva, Elena I.
Butranova, Olga I.
Kondakova, Yulia A.
author_facet Zyryanov, Sergey K.
Ushkalova, Elena A.
Kondratyeva, Elena I.
Butranova, Olga I.
Kondakova, Yulia A.
author_sort Zyryanov, Sergey K.
collection PubMed
description (1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransformation. (2) Materials and Methods: a two-center prospective non-randomized study of CPF pharmacokinetics with sequential enrollment of patients (n-33, mean age 9.03 years, male-33.36%), over a period from 2016 to 2021. All patients received tablets of the original CPF drug Cyprobay(®) at a dose of 16.5 mg/kg to 28.80 mg/kg. Blood sampling schedule: 0 (before taking the drug), 1.5 h; 3.0 h; 4.5 h; 6.0 h; 7.5 h after the first dosing. CPF serum concentrations were analyzed by high performance liquid chromatography mass spectrometry. The genotype of biotransformation enzymes was studied using total DNA isolated from whole blood leukocytes by the standard method. (4) Results: a possible relationship between the CA genotype of the CYP2C9 gene (c.1075A > C), the GG genotype of the CYP2D6*4 gene (1846G > A), the AG genotype of the GSTP1 gene (c.313A > G), the GCLC* genotype 7/7 and the CPF concentration in plasma (increased value of the area under the concentration–time curve) was established. Conclusions: Gene polymorphism of biotransformation enzymes may affect ciprofloxacin pharmacokinetics in children.
format Online
Article
Text
id pubmed-9139162
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-91391622022-05-28 Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis Zyryanov, Sergey K. Ushkalova, Elena A. Kondratyeva, Elena I. Butranova, Olga I. Kondakova, Yulia A. Biomedicines Article (1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransformation. (2) Materials and Methods: a two-center prospective non-randomized study of CPF pharmacokinetics with sequential enrollment of patients (n-33, mean age 9.03 years, male-33.36%), over a period from 2016 to 2021. All patients received tablets of the original CPF drug Cyprobay(®) at a dose of 16.5 mg/kg to 28.80 mg/kg. Blood sampling schedule: 0 (before taking the drug), 1.5 h; 3.0 h; 4.5 h; 6.0 h; 7.5 h after the first dosing. CPF serum concentrations were analyzed by high performance liquid chromatography mass spectrometry. The genotype of biotransformation enzymes was studied using total DNA isolated from whole blood leukocytes by the standard method. (4) Results: a possible relationship between the CA genotype of the CYP2C9 gene (c.1075A > C), the GG genotype of the CYP2D6*4 gene (1846G > A), the AG genotype of the GSTP1 gene (c.313A > G), the GCLC* genotype 7/7 and the CPF concentration in plasma (increased value of the area under the concentration–time curve) was established. Conclusions: Gene polymorphism of biotransformation enzymes may affect ciprofloxacin pharmacokinetics in children. MDPI 2022-05-02 /pmc/articles/PMC9139162/ /pubmed/35625789 http://dx.doi.org/10.3390/biomedicines10051050 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zyryanov, Sergey K.
Ushkalova, Elena A.
Kondratyeva, Elena I.
Butranova, Olga I.
Kondakova, Yulia A.
Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title_full Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title_fullStr Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title_full_unstemmed Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title_short Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis
title_sort gene polymorphism of biotransformation enzymes and ciprofloxacin pharmacokinetics in pediatric patients with cystic fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9139162/
https://www.ncbi.nlm.nih.gov/pubmed/35625789
http://dx.doi.org/10.3390/biomedicines10051050
work_keys_str_mv AT zyryanovsergeyk genepolymorphismofbiotransformationenzymesandciprofloxacinpharmacokineticsinpediatricpatientswithcysticfibrosis
AT ushkalovaelenaa genepolymorphismofbiotransformationenzymesandciprofloxacinpharmacokineticsinpediatricpatientswithcysticfibrosis
AT kondratyevaelenai genepolymorphismofbiotransformationenzymesandciprofloxacinpharmacokineticsinpediatricpatientswithcysticfibrosis
AT butranovaolgai genepolymorphismofbiotransformationenzymesandciprofloxacinpharmacokineticsinpediatricpatientswithcysticfibrosis
AT kondakovayuliaa genepolymorphismofbiotransformationenzymesandciprofloxacinpharmacokineticsinpediatricpatientswithcysticfibrosis