Chronic kidney disease and physiologically based pharmacokinetic modeling: a critical review of existing models

INTRODUCTION: Physiologically based pharmacokinetic (PBPK) modeling is a paradigm shift in this era for determining the exposure of drugs in pediatrics, geriatrics, and patients with chronic diseases where clinical trials are difficult to conduct. AREAS COVERED: July 2023 for identifying the relevant studies that met the inclusion/exclusion criteria. Alterations in plasma protein (albumin/alpha-1 acid glycoprotein), gastric emptying time, hematocrit, small intestinal transit time, the abundance of cytochrome (CYP) 450 enzymes, glomerular filtration rate, and physicochemical parameters for different drugs were explicitly elaborated from earlier reported studies. Moreover, model evaluation depicted that models in CKD for most of the included drugs were within the allowed two-fold error range. EXPERT OPINION: This review will provide insights for researchers on applying PBPK models in managing patients with different levels of CKD to prevent undesirable side effects and increase the effectiveness of drug therapy.