RE: Question about interoccation variability

From: [email protected] [mailto:[email protected]] On Behalf Of Xu, Claire Sent: Tuesday, July 10, 2012 4:46 PM To: [email protected] Subject: [NMusers] Question about interoccation variability Hi, everyone: I am trying to develop a pop PK model for a compound with a large variability in absorption. I have difficulty in fitting the absorption phase, especially the Cmax. Some of the subjects are underpredicted while some subjects are overpredicted. Since the study is a four-way cross-over study with 5 different occasions, I am thinking about incorporating interoccasion variability (IOV) on Ka in my model. I tried to test IOV using the code: IF OCC==1 BOVKA=ETA(1) ... IF OCC==5 BOVKA=ETA(5) KA=THETA(1)*EXP(BOVKA) $OMEGA BLOCK (1); for OCC=1 0.16 $OMEGA BLOCK(1) SAME; for OCC=2 ... $OMEGA BLOCK(1) SAME; for OCC=5 But it didn't improve the fitting. Then I tried to remove the "SAME" and five different estimation of ETAs were obtained. The fitting wasn't really improved. Can anyone comment on that whether it is oaky to have 5 different ETAs on one parameter in the model according to different occasions? Also, is there any suggestion to improve the fitting of absorption? I also tried ALAG model but not improve the fitting either. The Ka is kind of large for my compound (around 1.5). some of the subjects have the first sample as Cmax but not in other subjects. some of the subjects showed a second peak during distribution in some occasions but not in other occasions. Not sure how to handle all these visibilities in my data and get the good fit of absorption phase. Any suggestions would be appreciated. Thanks! Best, -- Xu, Claire Ph.D Candidate Division of Clinical Pharmacology, Wishard Hospital Indiana University School of Medicine 1001 West 10th Street, Myers W7122 Indianapolis, IN 46202 T - 317/7558242 This electronic transmission may contain confidential and/or proprietary information and is intended to be for the use of the individual or entity named above. If you are not the intended recipient, be aware that any disclosure, copying, distribution or use of the contents of this electronic transmission is prohibited. If you have received this electronic transmission in error, please destroy it and immediately notify us of the error. Thank you.