ABSTRACT
Effective and safe pharmacotherapy (drug and dose selection) following perinatal asphyxia necessitates integration of the available pieces of knowledge on (patho)physiology, further modulated by therapeutic interventions such as whole-body hypothermia. This review discusses the impact of maternal-to-fetal pH and hypoxia on placental-fetal and neonatal pharmacokinetics and dynamics respectively, with specific emphasis on the impact of asphyxia and its treatment, whole-body hypothermia.
This will be followed by a discussion to illustrate how pathophysiological characteristics and in vitro observations specific to this population can be integrated to create prediction tools (physiology-based pharmacokinetics, PB-PK), to subsequently explore their performance using available concentration-time profiles. At present, such PBPK tools are already used to generate predictions up to the level to support pivotal decisions during drug development and acceptance by regulatory authorities. Consequently, the novelty is not in the tool, but in the integration of available pieces of knowledge, and unveiling knowledge gaps in neonates with undergoing therapeutic hypothermia because of neonatal hypoxic ischemic encephalopathy. Such tools are not only relevant to adapt dosing of currently used drugs but are also relevant to support drug development to attain precision medicine in this specific population.
