Changing Clearance over time : Enzyme auto-induction

From: Partha Nandy partha.nandy@bms.com Subject:[NMusers] Changing Clearance over time : Enzyme auto-induction Date: Fri, August 6, 2004 2:46 pm Hi All, I am trying to model the kinetics of a drug that exhibits enzyme auto-induction. From the data it seems that for the first few days there is no effect on the enzyme, as evidenced from the accumulation factor. But slowly the induction sets in. To model the change in clearance, I am using a Emax model for CL; CL=CL0+CLmax*t/t50+t. I have used appropriate hill function as well, but my predicted concentrations are systematically lower than those observed at the earlier time points. Can any one help me with modeling the CL where the CL value will remain constant up to a time 'X', the critical time (preferably expressed as THETA) after which the non-linear function will kick-in. Your help is greatly appreciated. Regards, Partha Partha Nandy Clinical Discovery BMS-Lawrenceville, NJ