抄録
Pharmacokinetics (PK) has been the heart and soul of the discipline of clinical pharmacology. One of the reasons is because PK parameters provide key information necessary to design dosing schedules. Although the clinical relevance of PK information is evident, basic understanding of PK principles among clinicians remains poor, which highlights an important education role clinical pharmacologists need to play. The lack of the general understanding compromises appropriate clinical application of PK data to clinical practice particularly in special populations including infants and children. Difficulties in conducting conventional PK studies in children further intensify their therapeutic orphan status, causing rampant off-label/off-evidence uses of drug. Although the value of population PK allowing opportunistic sampling schedules to circumvent the conventional tight- scheduled sampling-intensive PK methods is widely recognized and advocated for infants and children, consistent efforts need to be made, so that PK information becomes available in a timely manner for this vulnerable population. The pediatric population is characterized by its remarkable transformation from a cluster of cells in the embryonic stage to a mature adult. The developmental trajectory is the hallmark of infants and children, which also poses challenges in PK data acquisition and interpretation. In the neonatal period, drug clearance per body weight (BW) or body surface area (BSA) is generally lower than in the older age groups. Over the following infantile period, drug clearance/BW consistently increases with variable rates among individuals and drugs in question. Specifically, drug-metabolizing enzymes such as CYP3A show relatively developed-expression patterns in the neonatal period, but CYP1A2 takes one year or more to reach an adult level of expression and function per BW or BSA. Due to increased water compartments per BW in the neonatal period, volume of distribution per BW of hydrophilic drugs is larger in this age group than in older age groups. Although the average pictures of these developmental profiles of PK can be described clearly, variations among drugs and individuals along the developmental trajectory are poorly understood. Application of physiologically-based PK modeling may be a first step to deepen our understanding of PK developmental profiles and its variations in the paediatric population.
