Dear Varsha, Did you evaluate the clearances as a continuous variable with changing temperature. I suspect that the hypothermia induced was not constant over the entire period so there may be a temperature dependent effect over the slices of time observed with this information. I have taken the liberty of copying Professor Poloyac at the University of Pittsburgh. This group has been extensively involved in evaluating hypothermia effects on clearance.
Best Regards, Rob Robert R. Bies Pharm.D.Ph.D. Associate Professor of Medicine and Medical Genetics Division of Clinical Pharmacology Member Center for Computational Biology and Bioinformatics Indiana University School of Medicine 1001 W 10th Street W7138 Indianapolis, IN 46202 317-630-7868 (office) 317-630-8185 (fax) -----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Varsha Mehta Sent: Friday, February 05, 2010 8:58 AM To: [email protected] Subject: [NMusers] Dilemma with PPK parameters Dear Group: I am seeking some help to logically explain the difference in CL of a drug between 2 groups who received the same drug for the same indication but one group had induced hypothermia (treatment-N=24) while the other did not (control-N=115). The half life for control- 111hrs and treatment 129 hrs (roughly)- not statistically different. However, the parameters: Control Group Treatment group CL- 0.000105 L/kg/hr (suspect) CL- 0.00467 L/kg/hr Vd -0.733 L/kg Vd 0.876 L/Kg I used the same model for both groups and the half life calc was part of the model. I have run the model for both multiple times using various theta values. each time the minimization is complete. The bootstrap for treatment group gives reasonably good agreement. The bootstrap for control parameters match well for Cl (0.000273 L/kg/hr) but not for Vd (0.416 L/kg). Given the relationship between Vd and CL how is this possible? How can the half life be so close when there is such a huge difference in CL for both groups? Where am I going wrong? Would appreciate any help anyone can provide. Thanks!! Varsha Mehta, MS(CRDSA), Pharm.D., FCCP Clinical Associate Professor Pharmacy, Pediatrics and Communicable Diseases Clinical Pharmacist Neonatal Critical Care University of Michigan (O) 734-936-8985 (F) 734-936-6946 [email protected] ********************************************************** Electronic Mail is not secure, may not be read every day, and should not be used for urgent or sensitive issues
