Abstract
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: This review has collated data regarding published PBPK models on chronic kidney disease (CKD), including the drug and system-specific input model parameters and model evaluation criteria. Four databases were used from 13th June 2023 to 10th 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.
Keywords: Chronic kidney disease (CKD); model evaluation; pathophysiology; pharmacokinetics; physiologically based pharmacokinetic modeling (PBPK); renal clearance.
https://pubmed.ncbi.nlm.nih.gov/38270999/ Expert Opin Drug Metab Toxicol. 2024 Jan-Feb;20(1-2):95-105. Ammara Zamir, Faleh Alqahtani, Muhammad Fawad Rasool
Abstract 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: This review has collated data regarding published PBPK models on chronic kidney disease (CKD), including the drug and system-specific input model parameters and model evaluation criteria. Four databases were used from 13th June 2023 to 10th 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.
Keywords: Chronic kidney disease (CKD); model evaluation; pathophysiology; pharmacokinetics; physiologically based pharmacokinetic modeling (PBPK); renal clearance.