The metabolism and disposition of drugs in the whole animal is a complex process sensitive to a wide variety of parameters as age, sex, nutritional status, and pretreatment with drugs. Although these parameters have been well defined in whole organisms and isolated microsomes, few studies have been reported in which these phenomenon have been investigated in a system which can respond to a variety of manipulations, but which is no longer under the influence of the body's homeostatic mechanism. To circumvent this problem, we have investigated the applicability of the isolated hepatocyte. In our continuing studies of this system we wish to: 1) further define the conditions for optimal metabolism, 2) to investigate several indices of metabolism to determine which of these are the most sensitive to the manipulation of the incubation medium, 3) investigate the kinetics of drug metabolism to assess how the various manipulations alter the kinetic parameters, 4) determine whether the transport process is saturable or not and if it is saturable whether it is active or passive, 5) correlate the structure-activity relationships for the transport process to define the chemical nature of the mechanism involved, and 6) to determine the effect of inducing agents and ethanol on the isolated hepatocyte. An understanding of metabolism is valuable in clinical investigations where it is important to be cognizant of which indices must be monitored to establish dosage regimens.
NIH ExPorter
NIH ExPorter