Dear Claire,
Through your constraint on THETA(5), you have restricted the mixture model to have MIXNUM=2 as the dominating (>=50%) subpopulation. I think this may result in your run ending up in a local minimum. I wouldn't be surprised if THETA(5) is driven towards zero. If you want to keep this parameterization for P(1), maybe you should try switching initial est's between THETA3 and THETA4. Best regards, Mats Mats Karlsson, PhD Professor of Pharmacometrics FIRST WORLD CONFERENCE ON PHARMACOMETRICS, 5-7 September 2012, Seoul ( <http://www.go-wcop.org/> www.go-wcop.org) Dept of Pharmaceutical Biosciences Faculty of Pharmacy Uppsala University Box 591 75124 Uppsala Phone: +46 18 4714105 Fax + 46 18 4714003 From: owner-nmus...@globomaxnm.com [mailto:owner-nmus...@globomaxnm.com] On Behalf Of Xu, Claire Sent: 23 July 2012 20:45 To: nmusers@globomaxnm.com Subject: [NMusers] Question about mixture model of Ka Hi Dear nmusers, I am trying to develop a pop PK model. In my data, there are two subpopulations, one subpopulation with Ka of about 9 and the other one with Ka of about 1. The percentage of population with higher Ka is about 15%. I assumed that it would be reasonable to utilize mixture model of Ka. But I cannot get the mixture model of Ka successfully run under NONMEM, because the percentage of the subpopulation can't be estimated. Can anyone help check my NONMEM code? Is there anything special that I should do for the input data profile? .I will very appreciateit it for your generous help. Thanks a lot! Claire $SUB ADVAN2 TRANS2 $PK CL=THETA(1)*EXP(ETA(1)) V=THETA(2)*EXP(ETA(2)) EST=MIXEST IF (MIXNUM==1) THEN ; pop1 KA=THETA(3)*EXP(ETA(3)) ELSE KA=THETA(4)*EXP(ETA(4)) ; pop2 ENDIF S2=V/1000 ; convert concentration to ng/ml $MIX NSPOP=2 A=EXP(THETA(5)) DEN=1+A P(1)=1/DEN ;pop1 P(2)=A/DEN ;pop2 $ERROR DEL = 0.0001 IPRED = LOG(DEL) IF (F.GT.DEL) IPRED = LOG(F) W=THETA(6) IRES=IPRED-DV IWRES = IRES/W Y=IPRED+EPS(1)*W $THETA (0,50) ;CL (0,550); V (0,1.5);KA for pop 1 (0,6); KA for pop 2 (0,1); per (0,0.16);W $OMEGA BLOCK(2) 0.16 0.01 0.16 $OMEGA 0.16 0.16 -- 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 <tel:317%2F7558242>
