Age peculiarities of pharmacotherapy with amoxicillin preparations in children with cystic fibrosis

Amoxicillin and amoxicillin/clavulanate are the medicines of choice for the treatment of infections caused by Staphylococcus aureus and Haemophilus influenzae in children with cystic fibrosis (CF) n the Russian Federation. However, pharmacokinetics (PK) of amoxicillin for CF in childhood was never studied. Objective of the research: To study the pharmacokinetic parameters of amoxicillin in different age periods in children with CF. Materials and methods: 19 patients with CF aged from 2 to 16 years took part in the study. After taking the medicine in mean dose of 31,25 mg/kg (from 28 to 34,5 mg/kg), blood was taken every 1,5 hours after a single dose for 7,5 hours. Pharmacokinetic parameters were assessed using the non-compartmental method in three age subgroups: 2-5 years, 6-11 years, and 12-16 years. Results: High interindividual variability of studied PK parameters was revealed. The lowest values of median AUC0-t, μg*h/ml and AUC0-t norm (μg*h/ml)/(mg/kg) (11,34 and 0,4, respectively) were in the subgroup of children aged 2-5 years. The highest values of median AUC0-t, μg*h/ml and AUC0-t norm (μg*h/ml)/(mg/kg) (18,45 and 0,64, respectively) were in the subgroup of 12-16 years old adolescents with CF. Values of Cmax (μg/ml) and Cmax norm (μg/ml)/(mg/kg) in the younger age group median were 2,79 μg/ml and 0,1 (μg/ml)/(mg/kg), in adolescent subgroup-5,47 μg/ml and 0,16 (μg/ml)/(mg/kg), respectively. Median time to reach maximum amoxicillin concentration in blood plasma in the subgroup of children aged 2-5 years with CF was 1,5 hours (1,5-3 hours); in subgroups of 6-11 years and 12-16 years, the median was estimated as 3 hours. Conclusion: Considering the results obtained, it can be assumed that, on average, the total clearance of amoxicillin decreases with age. Further studies of PC/pharmacodynamics are needed to develop adequate dosing regimens of amoxicillin for CF, especially in the group of children under 5 years of age. © 2019, Pediatria Ltd.. All rights reserved.

Авторы
Kondratieva E.I.1, 2 , Kondakova Y.A.3 , Zyryanov S.K. 4 , Bondareva I.B. 4 , Voronkova A.Y.1, 2 , Sherman V.D.1, 2 , Melyanovskaya Y.L.1, 2 , Odinayeva N.D.2 , Dronov I.A.5
Номер выпуска
4
Язык
Русский
Страницы
179-188
Статус
Опубликовано
Том
98
Год
2019
Организации
  • 1 Academician N.P. Bochkov Research Centre of Medical Genetics (RCMG) of the Russian Academy of Sciences, Moscow, Russian Federation
  • 2 Moscow Regional Consultative-Diagnostic Center for Children, Russian Federation
  • 3 City Children’s Clinical Emergency Hospital, Novosibirsk, Russian Federation
  • 4 Peoples’ Friendship University of Russia, Russian Federation
  • 5 I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
Ключевые слова
Amoxicillin; Amoxicillin/clavulanate; Children; Cystic fibrosis; Pharmacodynamics; Pharmacokinetics; Staphylococcus aureus; Нemophilus influenzae
Дата создания
24.12.2019
Дата изменения
24.12.2019
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/55187/