Профилактика кровотечений и фармакокинетика фактора свертывания крови VIII у детей с тяжелой гемофилией А

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Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2016; 15: 19-22

Профилактика кровотечений и фармакокинетика фактора свертывания крови VIII у детей с тяжелой гемофилией А

Дмитриев Вячеслав Васильевич, Волкова Людмила Ивановна, Дмитриев Евгений Вячеславович

https://doi.org/10.24287/1726-1708-2016-15-3-19-22

Аннотация

Для индивидуального выбора дозы и расчета кратности профилактического введения концентрата фактора свертывания VIII 23 пациентам с тяжелой гемофилией А проведено фармакокинетическое исследование. Период полураспада экзогенного фактора VIII, равный 12 часам, зарегистрирован у 12 (52%) пациентов, у 7 мальчиков (30%) период полураспада фактора VIII был 18 ч, у 4 (18%) детей - 11 ч. Индивидуальный фармакокинетический расчет позволил проводить вторичную профилактику спонтанных кровотечений с кратностью систематического введения концентрата фактора свертывания крови VIII через 72, 96 или 48 ч соответственно, без геморрагических осложнений. Сочетанное изменение таких параметров, как повышение клиренса (Cl) до 5,3 (4,3-5,6) мл х кг^-1 х час^-1, объема распределения (Vd) до 79,0 (75,0-83,0) мл х кг^-1 на фоне снижения нормализованного показателя площади под фармакокинетической кривой (AUC_norm) до 14,7 (10,0-23,0) мл^-1 х час х кг, показателя восстановления (Recovery in vivo) до 1,27 (1,2-1,32)% / ME х кг^-1 и периода полураспада (T/) до 11,0 (10,5-11,9) ч, характеризует ингибиторный типа ответа на введение концентрата фактора свертывания крови VIII.

Список литературы

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Pediatric Hematology/Oncology and Immunopathology. 2016; 15: 19-22

Secondary prevention of hemorrhagic complications and pharmacokinetics of factor VIII in children with severe hemophilia A

Dmitriev Vyacheslav V., Volkova Ludmila I., Dmitriev Evgeniy V.

https://doi.org/10.24287/1726-1708-2016-15-3-19-22

Abstract

Individual selection of dose and calculation of ratio for prevention of the introduction of the concentrate of coagulation factor VIII 23 patients with severe hemophilia A carried out the pharmacokinetic study. The half-life of exogenous factor VIII is 12 hours, registered in 12 (52%) patients, 7 boys (30%) - the half-life of factor VIII was 18 hours, in 4 (18%) children - 11 hours. Individual pharmacokinetic calculations allowed to carry out secondary prevention of spontaneous bleeding with multiplicity systematic introduction of a concentrate of coagulation factor VIII in 72, 96, or 48 hours, respectively, without bleeding complications. The combined change in parameters such as higher clearance (Cl) to 5,3 ml х kg^-1 х hour^-1, volume of distribution (Vd) to 79.0 ml х kg^-1 with the decline in the normalized measure of the area under the curve (AUCnorm) to 14.7 ml^-1 х h х kg and the recovery index (Recovery in vivo) to 1.27 % / ME х kg^-1 and half-life (T/) to 11.0 hours, characterizes a type of inhibitory response to the introduction of the concentrate of coagulation factor VIII.

References

3. Björkman S. Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective. Haemophilia. 2003;9(Suppl. 1):101-8; discussion 109-10.

6. Björkman S, Berntorp E. Pharmacokinetics of coagulation factors: clinical relevance for patients with haemophilia. Clin Pharmacokinet. 2001 ;40(11): 815-32.

Профилактика кровотечений и фармакокинетика фактора свертывания крови VIII у детей с тяжелой гемофилией А

Аннотация

Secondary prevention of hemorrhagic complications and pharmacokinetics of factor VIII in children with severe hemophilia A

Abstract

События