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OP-146 Personalized prescription of antibacterial therapy for children with cystic fibrosis (pharmacokinetic and pharmacogenetic studies)
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  1. Vera Shadrina1,
  2. Yulia Kondakova2,
  3. Elena Kondratyeva3,
  4. Sergey Zyryanov4
  1. 1Research Clinical Institute of Childhood of the Ministry of Health of Moscow Region
  2. 2City Children’s Clinical Hospital of Emergency Medical Care, Novosibirsk
  3. 3Medical Genetic Research Center named after Academician N.P. Bochkov
  4. 4Peoples’ Friendship University of Russia

Abstract

Aim to study the effect of age on the pharmacokinetic parameters (PP) of amoxicillin and ciprofloxacin in cystic fibrosis (CF) children.

Material and Method Аmoxicillin used at an average dose 31.25 mg/kg to CF children (n=19) 2 -18 y.o., ciprofloxacin - 19.91 mg/kg (n=33). Serum concentrations of аmoxicillin and ciprofloxacin were assessed every 1.5 hours for 7.5 hours. PP were assessed in ages subgroups: 2–6, 6–12, 12–18 years. PP of ciprofloxacin were studied in patients with the different polymorphisms of biotransformation genes.

Results The lowest values of the median (Me) AUC(0-t), μg.h/ml and AUC0-t norm, (μg.h/ml)/(mg/kg) were 11.34 and 0.40, respectively for аmoxicillin; 67.73 and 2, 89 - for ciprofloxacin in children 2–6 years. The highest values of the Me AUC0-t, μg.h/ml and AUC0-t norm, (μg.h/ml)/(mg/kg) 18.45 and 0.64, respectively for аmoxicillin; 80.73 and 4.24 - for ciprofloxacin were in a adolescents. Me of Cmax (µg/ml) and Cmax norm (µg/ml)/(mg/kg) in children 6–12 years were 2.79 and 0.10 for аmoxicillin; 18.31 and 0.83 - for ciprofloxacin, in the adolescents - 5.47 and 0.16 for аmoxicillin; 19.79 and 0.99 - for ciprofloxacin. The Me Tmax of аmoxicillin of children 2–6 years was 1.5 h., in older children - 3 h. For ciprofloxacin – 1.5 h. in children 2–6 years and 4.5 h. - in children 12–18 years. In patients with genotypes CA for the CYP2C9 gene(I359L, c.1075A>C), AG and GG for the GSTP1 (c.313A>G), 7/7 of the GCLC, higher values of the PP of ciprofloxacin were observed.

Conclusions In patients aged 2–6 years, the PP of antibiotics were higher than in older children. In patients with normal or rapid polymorphisms of phase 1 and phase 2 biotransformation genes, there is a risk of the insufficient plasma concentration of the antibiotic.

  • cystic fibrosis
  • аmoxicillin
  • ciprofloxacin
  • pharmacogenetics
  • pharmacokinetics

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