Plasma Concentrations of Oseltamivir and Oseltamivir Carboxylate in Critically Ill Children on Extracorporeal Membrane Oxygenation Support

被引:33
作者
Wildschut, Enno D. [1 ]
de Hoog, Matthijs [1 ,2 ]
Ahsman, Maurice J. [3 ]
Tibboel, Dick [1 ]
Osterhaus, Albert D. M. E. [4 ]
Fraaij, Pieter L. A. [1 ,4 ]
机构
[1] Erasmus MC Sophia Childrens Hosp, Dept Paediat Surg, Rotterdam, Netherlands
[2] Erasmus MC Sophia Childrens Hosp, Dept Paediat, Rotterdam, Netherlands
[3] Erasmus MC, Dept Hosp Pharm, Clin Pharmacol Unit, Rotterdam, Netherlands
[4] Erasmus MC, Dept Virol, Rotterdam, Netherlands
来源
PLOS ONE | 2010年 / 5卷 / 06期
关键词
2009 INFLUENZA A(H1N1); PRODRUG OSELTAMIVIR; A H1N1; PHARMACOKINETICS;
D O I
10.1371/journal.pone.0010938
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Introduction: To evaluate the effect of extracorporeal membrane oxygenation (ECMO) support on pharmacokinetics of oseltamivir and oseltamivir carboxylate (OC) in children. Methodology: Steady state 0-12 hour pharmacokinetic sampling was performed in new influenza A (H1N1) infected children treated with oseltamivir while on ECMO support. Cmax, Cmin and AUC(0-12) (h) were calculated. The age-specific oseltamivir dosage was doubled to counter expected decreased plasma drug concentrations due to increased volume of distribution on ECMO support. Principal Findings: Three patients were enrolled aged 15, 6 and 14 years in this pharmacokinetic case series. For two children the OC plasma concentrations were higher than those found in children and adults not on ECMO. These increased plasma concentrations related to the increased oseltamivir dosage and decreased kidney function. In one patient suboptimal plasma concentrations coincided with a decreased gastric motility. Conclusion: Oseltamivir pharmacokinetics do not appear to be significantly influenced by ECMO support. Caution is required in case of nasogastric administration and decreased gastric motility. Due to the limited number of (paediatric) patients available further multicenter studies are warranted.
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