10 research outputs found
Personalized Tacrolimus Dose Requirement by CYP3A5 but Not ABCB1 or ACE Genotyping in Both Recipient and Donor after Pediatric Liver Transplantation
Coronary dilatation 10 weeks after paclitaxel-eluting stent implantation. No role of shear stress in lumen enlargement?
Time Trends in Prevalence of Chronic Diseases and Multimorbidity Not Only due to Aging: Data from General Practices and Health Surveys
The POR rs1057868–rs2868177 GC-GT diplotype is associated with high tacrolimus concentrations in early post-renal transplant recipients
Urinary Neutrophil Gelatinase-Associated Lipocalin: A Useful Biomarker for Tacrolimus-Induced Acute Kidney Injury in Liver Transplant Patients
Effect of Kidney Function on Drug Kinetics and Dosing in Neonates, Infants, and Children
Neonates, infants, and children differ from adults in many aspects, not just in age, weight, and body composition. Growth, maturation and environmental factors affect drug kinetics, response and dosing in pediatric patients. Almost 80% of drugs have not been studied in children, and dosing of these drugs is derived from adult doses by adjusting for body weight/size. As developmental and maturational changes are complex processes, such simplified methods may result in subtherapeutic effects or adverse events. Kidney function is impaired during the first 2 years of life as a result of normal growth and development. Reduced kidney function during childhood has an impact not only on renal clearance but also on absorption, distribution, metabolism and nonrenal clearance of drugs. 'Omics'-based technologies, such as proteomics and metabolomics, can be leveraged to uncover novel markers for kidney function during normal development, acute kidney injury, and chronic diseases. Pharmacometric modeling and simulation can be applied to simplify the design of pediatric investigations, characterize the effects of kidney function on drug exposure and response, and fine-tune dosing in pediatric patients, especially in those with impaired kidney function. One case study of amikacin dosing in neonates with reduced kidney function is presented. Collaborative efforts between clinicians and scientists in academia, industry, and regulatory agencies are required to evaluate new renal biomarkers, collect and share prospective pharmacokinetic, genetic and clinical data, build integrated pharmacometric models for key drugs, optimize and standardize dosing strategies, develop bedside decision tools, and enhance labels of drugs utilized in neonates, infants, and children