Studying cytochrome P450 kinetics in drug metabolism.
BACKGROUND
Determination of cytochrome P450 enzyme-mediated kinetics in vitro can be useful for predicting drug dosing and clearance in humans. Expressed P450s, human liver microsomes, human hepatocytes (both fresh and cryopreserved), and human liver slices are used to estimate K(m) and V(max) values for determination of intrinsic clearance of the drug for scale-up to predict in vivo clearance.


OBJECTIVE
To describe the advantages and disadvantages of the various in vitro systems used to estimate kinetic parameters for disposition of drugs and the various kinetic profiles that can be observed.


METHODS
A review of the literature was conducted to evaluate the utility of the various in vitro preparations, the methods for determining kinetic parameters and the types of kinetic profiles that may be observed.


CONCLUSIONS
The choice of in vitro system for determining kinetic parameters will depend on the objective of the studies, as each system has advantages and disadvantages. Kinetic parameter determinations must be carefully assessed to assure that the correct kinetic model is applied and the most accurate kinetic parameters are determined.
Kramer
Melissa A
MA
University of Minnesota, College of Pharmacy, Department of Experimental and Clinical Pharmacology, 7-115B Weaver-Densford Hall, 308 Harvard Street SE, Minneapolis, MN 55455, USA.
Tracy
Timothy S
TS
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004798:Enzymes / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics
D004798:Enzymes; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System