Dear Dr. Holford: Please correct me if I am wrong, but I think the DV may not have been log transformed. If the DV was log transformed, the residual error model may have been coded as
IPRED=LOG(F) Y=LOG(F)+W*ERR(1) Dear Dr. Gibiansky: I think you may have used DV in the original units with an residual error model for log transformed DV, which is equivalent to an additional+proportional residual model. Please correct me if I am wrong. But would you please clarify a little bit why you used this error model instead of a regular additional+proportional residual model? Thanks! ------------ Kelong Han PhD Candidate University of Pittsburgh School of Pharmacy ________________________________________ From: [email protected] [[email protected]] On Behalf Of Nick Holford [[email protected]] Sent: Sunday, March 28, 2010 1:44 PM To: [email protected] Cc: [email protected] Subject: Re: [NMusers] Parallel first order and Michaelis-Menten elimination Leonid, Thanks for the code example which illustrates one side of a religious debate which took place a few weeks ago on PharmPK. The essence of this debate was should one normalize PK parameters to a unit volume or to a unit body. The unit volume believers feel that the rate constant is the 'natural' way to describe pharmacokinetics while the unit body believers feel that clearance is more 'natural'. Both groups agree that the two systems are just reparameterizations and make identical numerical predictions. Your coding of Vmax for the mixed order elimination process has the implicit units of mass/time per unit volume e.g. mg/h/L. This is the unit volume belief system. I am a unit body believer so I would code this system differently with a very simple change- substituting A(1) with C1 to multiply the mixed order expression. I have also changed VM to VMUB to indicate that the dimensions of the Vmax parameter are per unit body i.e. mg/h per body. DADT(1) = -K10*A(1)-C1*VMUB/(KM+C1)-K12*A(1)+K21*A(2) It could also be written like this to emphasize that the mixed order process has the same units as CL (for unit body believers) when C1 tends to 0: DADT(1) = -C1*(CL+VMUB/(KM+C1) - K12*A(1)+K21*A(2) I note also that your residual error model implies that the DV has been log transformed. This reflects yet another belief system which I think you have shown has little, if any, practical merit. I prefer to keep the DV in the original units. Best wishes, Nick Leonid Gibiansky wrote: ADVAN6 ADVAN8 or (nm7) ADVAN13 The code is below Leonid ------------------- $SUBROUTINE ADVAN6 TOL=9 $MODEL NCOMP = 2 COMP = (CENTRAL) ;1 COMP = (PERIPH) ;2 $PK CL= THETA(1)*EXP(ETA(1)) V1= THETA(2)*EXP(ETA(2)) Q = THETA(3)*EXP(ETA(3)) V2= THETA(4)*EXP(ETA(4)) VM= THETA(5)*EXP(ETA(5)) KM= THETA(6) K10 = CL/V1 K12 = Q/V1 K21 = Q/V2 S1 = V1 S2 = V2 $DES C1 = A(1)/S1 DADT(1) = -K10*A(1)-A(1)*VM/(KM+C1)-K12*A(1)+K21*A(2) DADT(2) = K12*A(1)-K21*A(2) $ERROR TY = A(1)/V1 IPRED=TY W = SQRT(THETA(7)**2/TY**2+THETA(8)**2) Y = IPRED*EXP(W*ERR(1)) $THETA ..... $OMEGA ..... $SIGMA 1 FIX ; ~ERR -------------------------------------- Leonid Gibiansky, Ph.D. President, QuantPharm LLC web: www.quantpharm.com<http://www.quantpharm.com> e-mail: LGibiansky at quantpharm.com tel: (301) 767 5566 [email protected]<mailto:[email protected]> wrote: Dear All, I am working with a Biologic and would like to have a PK model with parallel first order and Michaelis-Menten elimination. Any suggestion about which subroutine I am supposed to use? If you can share an example for the control stream, that will be a great help. Thanks, Yuhong -- Nick Holford, Professor Clinical Pharmacology Dept Pharmacology & Clinical Pharmacology University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53 email: [email protected]<mailto:[email protected]> http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
