TY - JOUR T1 - Ontogeny and cross species comparison of pathways involved in drug absorption, distribution, metabolism and excretion in neonates (Review): KIDNEY JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.119.089755 SP - dmd.119.089755 AU - Ruud Bueters AU - An Bael AU - Elke Gasthuys AU - Connie Chen AU - Michiel F Schreuder AU - Kendall S Frazier Y1 - 2020/01/01 UR - http://dmd.aspetjournals.org/content/early/2020/02/29/dmd.119.089755.abstract N2 - The kidneys play an important role in many processes, including urine formation, water conservation, acid-base equilibrium, and elimination of waste. The anatomical and functional development of the kidney has different maturation time points in humans versus animals, with critical differences between species in maturation before and after birth. Absorption, distribution, metabolism and excretion (ADME) of drugs vary depending on age and maturation, which will lead to differences in toxicity and efficacy. When neonate/juvenile laboratory animal studies are designed, a thorough knowledge of the differences in kidney development between newborns/children and laboratory animals is essential. The human and laboratory animal data must be combined to obtain a more complete picture of the development in the kidneys around the neonatal period and the complexity of ADME in newborns and children. This review examines the ontogeny and cross-species differences in ADME processes in the developing kidney in preterm and term laboratory animals and children. It provides an overview of insights into ADME functionality in the kidney by identifying what is currently known and which gaps still exist. Important renal function properties such as glomerular filtration rate, renal blood flow and ability to concentrate are generally well known, detailed knowledge about transporter and metabolism maturation is growing, but is still lacking. Preclinical data in those properties is limited to rodents and generally covers only the expression levels of transporter or enzyme-encoding genes. More knowledge on a functional level is needed to predict the kinetics and toxicity in neonate/juvenile toxicity and efficacy studies.SIGNIFICANCE STATEMENT This review provides insight in cross-species developmental differences of ADME properties in the kidney, which should be considered in neonate/juvenile study interpretation, hypotheses generation and experimental design. ER -