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.