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.
Highlights
For citation: Rodionov GG, Shantyr’ II, Vasilyuk VB, Kolobova EA, Svetkina EV, Faraponova MV, Verveda AB, Syraeva GI, Zakharov KA
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
Подбор индивидуального курса терапии пациентов с В-клеточным хроническим лимфолейкозом препаратом с международным непатентованным наименованием (МНН) флударабин целесообразно осуществлять на основании учёта гендерно-антропометрических характеристик и математического моделирования показателей фармакокинетики активного метаболита флударабин фосфата
Summary
For citation: Rodionov GG, Shantyr’ II, Vasilyuk VB, Kolobova EA, Svetkina EV, Faraponova MV, Verveda AB, Syraeva GI, Zakharov KA. Результаты измерения концентрации 2-фторара-А в плазме крови пациентов с В-клеточным хроническим лимфолейкозом при однократном приёме перорально препарата с МНН флударабин в дозе 40 мг/м2 представлена на рис. 1. Усреднённые значения концентрации 2-фтор-ара-А в плазме крови пациентов с В-клеточным хроническим лимфолейкозом при однократном приёме перорально препарата с МНН флударабин в дозе 40 мг/м2 Figure 1.
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