Individual features of the pharmacokinetics of fludarabin phosphate in the treatment of patients with chronic lymphocytic leukemia-Reference-Cited by-同舟云学术

Individual features of the pharmacokinetics of fludarabin phosphate in the treatment of patients with chronic lymphocytic leukemia

Published:2021-08-13 Issue:2 Volume: Page:67-77
ISSN:2618-8473
Container-title:Kachestvennaya Klinicheskaya Praktika = Good Clinical Practice
language:
Short-container-title:GCP

Author:

Rodionov G. G.¹^ORCID,Shantyr I. I.¹^ORCID,Vasilyuk V. B.²^ORCID,Kolobova E. A.¹^ORCID,Svetkina E. V.¹^ORCID,Faraponova M. V.³^ORCID,Verveda A. B.⁴^ORCID,Syraeva G. I.⁵^ORCID,Zakharov K. A.³

Affiliation:

1. The FSBI «The Nikiforov Russian Center of Emergency and Radiation Medicine», EMERCOM of Russia

2. The Limited Liability Company «Research center Eco-safety»; North-Western State Medical University named after I.I. Mechnikov

3. The Limited Liability Company «Research center Eco-safety»

4. The Limited Liability Company «Research center Eco-safety»; Golikov Research Center of Toxicology

5. The Limited Liability Company «Research center Eco-safety»; FSBEI HE I.P. Pavlov SPbSMU MOH Russia

Abstract

Fludarabine is a purine antimetabolite with a pronounced immunosuppressive effect. The inhibitory effect of fludarabine depends on its concentration in blood plasma. In addition, the phenotypic characteristics of patients affect the pharmacokinetic and pharmacodynamic profile of the drug, which necessitates a personalized approach to the dosage regimen. The chromatography-mass spectrometric method for the quantitative determination of 2-fluorine in blood plasma was developed for studying the individual parameters of pharmacokinetics of the international non-proprietary name (INN) fludarabine in patients with B-cell chronic lymphocytic leukemia during the standard course. Such method for the quantitative determination of 2-fluorine in blood plasma was developed and validated in accordance with international requirements. Significant individual variability of the main pharmacokinetic parameters in patients with B-cell chronic lymphocytic leukemia with a single oral administration of the drug with INN fludarabine at a dose of 40 mg/m2 was established, so the coefficient of variability Cmax was 42 %, Tmax — 92 %, AUC0-t — 45 %, Kel — 23 %, T1/2 — 26 %. It should be noted that there is a high interindividual variability of fludarabine, for example, 24 hours after taking the study drug, the maximum and minimum plasma concentrations of the fludarabine metabolite 2-fluoro-ara-A in different in patients with B-cell chronic lymphocytic leukemia differed 9 times. Individual variability of pharmacokinetic parameters characterizing absorption (Cmax/AUC0-t) and total clearance of the active metabolite of fludarabine is statistically significantly associated with a combination of gender and anthropometric factors.

Publisher

Publishing House OKI

Subject

General Medicine

Reference25 articles.

1. Baranov VS, Baranova EV, Ivashchenko TE, Aseev MV. Genom cheloveka i geny «predraspolozhennosti». Vvedenie v prediktivnuyu meditsinu. Saint Petersburg: Intermedika; 2000. (In Russ).

2. Kukes VG. Metabolizm lekarstvennykh sredstv: kliniko-farmakologicheskie aspekty. Moscow: Reafarm; 2004. (In Russ).

3. Kukes VG, Grachev SV, Sychev DA, Ramenskaya GV. Metabolizm lekarstvennykh sredstv: nauchnye osnovy personalizirovannoi meditsiny. Moscow: GEOTAR-Media; 2008. (In Russ).

4. The rules for conducting bioequivalence studies of medicinal products within the framework of the Eurasian Economic Union, approved by the Decision of the Council of the Eurasian Economic Commission of November 3, 2016 №. 85 Доступно по: http://docs.cntd.ru/document/456026107 Ссылка активна на 01.06.2021.

5. Bogni A, Monshouwer M, Moscone A, Hidestrand M, IngelmanSundberg M, Hartung T, Coecke S. Substrate specific metabolism by polymorphic cytochrome P450 2D6 alleles. Toxicol in Vitro. 2005:19(5):621-9. doi: 10.1016/j.tiv.2005.04.001.