A Semi-Physiologically Based Pharmacokinetic Pharmacodynamic Model for Glycyrrhizin-Induced Pseudoaldosteronism and Prediction of the Dose Limit Causing Hypokalemia in a Virtual Elderly Population

• Published in: PloS one Vol. 9; no. 12; p. e114049
• Main Authors: Xu, Ruijuan, Liu, Xiaoquan, Yang, Jin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.12.2014; Public Library of Science (PLoS)
• Subjects: Acids; Aldosterone; Angiotensin; Angiotensin II; Angiotensins; Animals; Biology and Life Sciences; Computer Simulation; Cortisol; Cortisone; Dehydrogenases; Drug dosages; Enzymes; Excretion; Exposure; Food additives; Geriatrics; Glycyrrhizic Acid - adverse effects; Glycyrrhizic Acid - pharmacokinetics; Glycyrrhizin; Hormones; Humans; Hypertension; Hypokalemia; Hypokalemia - chemically induced; Kidneys; Laboratories; Liddle Syndrome - chemically induced; Liddle Syndrome - metabolism; Male; Mathematical models; Medicine and Health Sciences; Metabolism; Metabolites; Microbiota; Monte Carlo Method; Monte Carlo methods; Monte Carlo simulation; Older people; Pharmaceuticals; Pharmacodynamics; Pharmacokinetics; Pharmacology; Plasma levels; Potassium; Probability distribution; Rats; Rats, Sprague-Dawley; Renin; Risk Assessment; Rodents; Scaling; Scaling factors; Sodium; China

Glycyrrhizin (GL) is a widely used food additive which can cause severe pseudoaldosteronism at high doses or after a long period of consumption. The aim of the present study was to develop a physiologically based pharmacokinetic (PBPK) pharmacodynamic (PD) model for GL-induced pseudoaldosteronism to...