*5.4. Metformin and Nisoldipine*

A whole-body PBPK model was also used to predict the pharmacokinetics of metformin in diabetic patients [153]. The results show that increased plasma levels of metformin following oral dose mainly resulted from both the impairment of renal function and delaying gastrointestinal transit. The metabolism of nisoldipine is mediated by CYP3As. Decreased CYP3A activity may partly explain the increased oral plasma exposure. However, when nisoldipine, in controlled-release tablets, was given to diabetic patients, the roles of gastrointestinal transit were nonnegligible. PBPK simulation also demonstrated that delaying gastrointestinal transit increased the intestinal absorption of nisoldipine, indicating that increased oral plasma of nisoldipine following oral administration of nisoldipine controlled-release tablet in diabetes patients was mainly attributed to both decreased CYP3As and delaying gastrointestinal transit.
