A semi-physiologically based pharmacokinetic pharmacodynamic model for glycyrrhizin-induced pseudoaldosteronism and prediction of the dose limit causing hypokalemia in a virtual elderly population.

ABSTRACT: 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 improve the safe use of GL. Since the major metabolite of GL, glycyrrhetic acid (GA), is largely responsible for pseudoaldosteronism via inhibition of the kidney enzyme 11β-hydroxysteroiddehydrogenase 2 (11β-HSD 2), a semi-PBPK model was first developed in rat to predict the systemic pharmacokinetics of and the kidney exposure to GA. A human PBPK model was then developed using parameters either from the rat model or from in vitro studies in combination with essential scaling factors. Kidney exp

SUBMITTER: Xu R 

PROVIDER: S-EPMC4252094 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature