Application of a physiologically based pharmacokinetic model to assess propofol hepatic and renal glucuronidation in isolation: utility of in vitro and in vivo data.

ABSTRACT: A physiologically based pharmacokinetic (PBPK) modeling approach was used to assess the prediction accuracy of propofol hepatic and extrahepatic metabolic clearance and to address previously reported underprediction of in vivo clearance based on static in vitro-in vivo extrapolation methods. The predictive capacity of propofol intrinsic clearance data (CLint) obtained in human hepatocytes and liver and kidney microsomes was assessed using the PBPK model developed in MATLAB software. Microsomal data obtained by both substrate depletion and metabolite formation methods and in the presence of 2% bovine serum albumin were considered in the analysis. Incorporation of hepatic and renal in vitro metabolic clearance in the PBPK model resulted in underprediction of propofol clearance regardless of

SUBMITTER: Gill KL 

PROVIDER: S-EPMC3608455 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature