Hi Varsha, In your control stream you have CL and Vd parameterized as:
TVCL = THETA(1) + THETA (3) * WT TVVD = THETA(2) + THETA (4) * WT Thus, THETA(1) and THETA(2) are the typical individual values of CL and Vd at WT=0 which are meaningless parameters. If both CL and Vd are directly proportional to WT then we would expect estimates of THETA(1) and THETA(2) to go to zero. I don't know how this control stream relates to the estimates you provide below because you don't have a covariate for treatment group on CL or Vd but I assume you are reporting estimates for THETA(3) and THETA(4). However, if your estimates of THETA(1) and THETA(2) are substantially different from zero between groups then this may be the explanation. If you use the following parameterization: TVCL = THETA(1) * WT TVVD = THETA(2) * WT I don't think you would see a disconnect. Of course, Nick would want you to use WT**0.75 for CL. Ken Kenneth G. Kowalski President & CEO A2PG - Ann Arbor Pharmacometrics Group, Inc. 110 E. Miller Ave., Garden Suite Ann Arbor, MI 48104 Work: 734-274-8255 Cell: 248-207-5082 Fax: 734-913-0230 ken.kowal...@a2pg.com -----Original Message----- From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Varsha Mehta Sent: Friday, February 05, 2010 8:58 AM To: nmusers@globomaxnm.com 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 vars...@umich.edu ********************************************************** Electronic Mail is not secure, may not be read every day, and should not be used for urgent or sensitive issues
