Introduction
Pediatric myocarditis is a common disease of cardiovascular system in
children [1]. It has become a serious threat to the life and health
of children owing to its complex clinical manifestations, rapidly
illness development and lacking of specificity diagnosis methods
[2].
Phosphocreatine (PCr) is an important endogenic high-energy phosphate
compound in the human or mammalian animals. It acts as a crucial part in
cellular energy metabolism by acting as an immediately temporal and
spatial energy buffer for the intracellular energy transport [3, 4].
PCr was metabolized into creatine (Cr) and generate ATP by creatine
kinase [5]. ATP consumption during myocardial injury is mainly
replenished by PCr transformation. At present, PCr could be obtained by
artificial synthesis. Exogenous complementary PCr is believed to help
solve the most fundamental problem of energy metabolism in damaged
myocardium and it has been used as a cardio-protective drug and applied
to the therapy of heart failure or myocardial infarction [6-9].
Exogenous PCr also has begun to be used in the therapy of pediatric
myocarditis [2]. In addition, it has also been recorded in the
Chinese National Formulary (page 212, the chemical and biological
products for children) and the Chinese Pharmacopoeia (2015), as the drug
for viral myocarditis. The pharmacokinetics (PK) of PCr in adults and
animals has already been studied [10-12]. After intravenous PCr in
mice, the changes of PCr concentrations were consistent with
two-compartment model and most of PCr are metabolized to Cr [10].
The PK studies of PCr in adults also showed that the elimination of PCr
in human body was two-phase elimination [11]. While, the
distribution of its major metabolite Cr in human body has not been
studied.
However, the currently available information about PCr in children was
limited which was considered as “off-label use”. The PK of PCr and Cr
in children is unknown and interindividual variability (IIV) is not
clear.
To resolve the above problems, the population pharmacokinetics of PCr
and its metabolite Cr in Chinese children was performed at Beijing
Children’s Hospital. This study was designed to understand the
pharmacokinetic behavior of PCr and Cr in children after intravenous
infusion and identify significant factors influencing PK parameters, so
as to provide evidence for rational use in children.