Clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir in children with cytomegalovirus infection

被引:46
作者
Stockmann, Chris [1 ,2 ,3 ]
Roberts, Jessica K. [1 ]
Knackstedt, Elizabeth D. [3 ]
Spigarelli, Michael G. [1 ,2 ]
Sherwin, Catherine M. T. [1 ]
机构
[1] Univ Utah, Sch Med, Dept Pediat, Div Clin Pharmacol, Salt Lake City, UT 84108 USA
[2] Univ Utah, Coll Pharm, Dept Pharmacol Toxicol, Salt Lake City, UT 84108 USA
[3] Univ Utah, Sch Med, Dept Pediat, Div Pediat Infect Dis, Salt Lake City, UT 84108 USA
关键词
antiviral; cytomegalovirus; pediatric; population pharmacokinetics; ORGAN TRANSPLANT RECIPIENTS; CELL-MEDIATED-IMMUNITY; CONTINUOUS VENOVENOUS HEMODIAFILTRATION; PROPHYLACTIC ORAL GANCICLOVIR; SENSORINEURAL HEARING-LOSS; SIMPLEX-VIRUS TYPE-1; EPSTEIN-BARR-VIRUS; CONTROLLED-TRIAL; POPULATION PHARMACOKINETICS; INTRAVENOUS GANCICLOVIR;
D O I
10.1517/17425255.2015.988139
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Introduction: Among infants and immunocompromised children cytomegalovirus (CMV) is associated with significant morbidity and mortality. Areas covered: This review describes the clinical pharmacokinetics and pharmacodynamics of ganciclovir and valganciclovir for the treatment and prevention of CMV infection in children. Expert opinion: A 24-h ganciclovir area under the concentration versus time curve (AUC(0 - 24)) of 40 - 60 mu g h/ml decreased the risk of CMV infection for adults undergoing CMV prophylaxis. For adults undergoing treatment for active CMV disease, a target AUC(0 - 12) of 40 - 60 mu g h/ml has been suggested. The applicability of these targets to children remains uncertain; however, with the most sophisticated dosing regimens developed to date only 21% of patients are predicted to reach these targets. Moving forward, identification of optimal pediatric ganciclovir and valganciclovir dosing regimens may involve the use of an externally validated pediatric population pharmacokinetic model for empirical dosing, an optimal sampling strategy for collecting a minimal number of blood samples for each patient and Bayesian updating of the dosing regimen based on an individual patient's pharmacokinetic profile.
引用
收藏
页码:205 / 219
页数:15
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