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Biomedicines
Volume 10
Issue 5
10.3390/biomedicines10051050
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Article

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

by
Sergey K. Zyryanov
1,2,
Elena A. Ushkalova
1,
Elena I. Kondratyeva
3,
Olga I. Butranova
1,* and
Yulia A. Kondakova
4
1
Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya Street, Moscow 117198, Russian Federation
2
Department of Health of the City of Moscow, City Clinical Hospital No. 24, State Budgetary Institution of the City of Moscow, Pistzovaya Str. 10, 127015 Moscow, Russia
3
Research Centre for Medical Genetics, 1 Moskvorechyie Str., 115522 Moscow, Russia
4
GBUZ NSO City Children’s Clinical Hospital of Emergency Medical Aid, Krasny Prospekt 3, 630007 Novosibirsk, Russia
*
Author to whom correspondence should be addressed.
Academic Editors: Jose-Bruno Montoro-Ronsano and Natalia Shnayder
Biomedicines 2022, 10(5), 1050; https://doi.org/10.3390/biomedicines10051050
Received: 30 March 2022 / Revised: 27 April 2022 / Accepted: 30 April 2022 / Published: 2 May 2022
(This article belongs to the Special Issue Pharmacokinetics of Biomedicines: Impact on Pre-clinical Development and Clinical Use)
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Abstract

(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. View Full-Text
Keywords: cystic fibrosis; children; ciprofloxacin; pharmacokinetics; biotransformation enzymes; genetic polymorphism cystic fibrosis; children; ciprofloxacin; pharmacokinetics; biotransformation enzymes; genetic polymorphism
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MDPI and ACS Style

Zyryanov, S.K.; Ushkalova, E.A.; Kondratyeva, E.I.; Butranova, O.I.; Kondakova, Y.A. Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis. Biomedicines 2022, 10, 1050. https://doi.org/10.3390/biomedicines10051050

AMA Style

Zyryanov SK, Ushkalova EA, Kondratyeva EI, Butranova OI, Kondakova YA. Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis. Biomedicines. 2022; 10(5):1050. https://doi.org/10.3390/biomedicines10051050

Chicago/Turabian Style

Zyryanov, Sergey K., Elena A. Ushkalova, Elena I. Kondratyeva, Olga I. Butranova, and Yulia A. Kondakova. 2022. "Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis" Biomedicines 10, no. 5: 1050. https://doi.org/10.3390/biomedicines10051050

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