Re: Predicted Concetration derivations

Date: Wed, 17 Nov 1999 13:57:22 -0800 (PST) From: ABoeckmann <alison@c255.ucsf.edu> Subject: Re: Predicted Concetration derivations I don't think the group can help with this. I'll respond only to the question about the 1st. control stream because the kinetics are so simple. Maybe this will be sufficient. Because Rebecca included the reparameterization from CL and V to rate constant K, she does not need to use TRANS2. It simply repeats the reparameterization. She could save some run time using ADVAN1 TRANS1, but this should not affect the outcome of the run. She does not show us her dosing records. Suppose there is only a single bolus dose AMT at T0. THen the calculation of A0, A1, A2 at event times T0, T1, T2, etc. is: A0=AMT A1=A0*EXP(-K*(T1-T0)) A2=A1*EXP(-K*(T2-T1)) The predictions PRED0, PRED1, PRED2, etc. at these event times are PRED0=A0/S1 PRED1=A1/S1 PRED2=A2/S1 With the default method of estimation, etas are 0. In the above, K=theta(1)/theta(2) S1=theta(2) If there are multiple bolus doses, they are added when appropriate. E.g., if there is a dose AMTi at time Ti, then Ai=Ai (from above)+AMTi If there are infusions, the equations are more complicated. I do not know why she cannot get the same values from "the modeling routines". But make sure that the thetas are the same. If REbecca is plugging in thetas derived from other routines into NONMEM, then DO NOT RUN THE ESTIMATION STEP!! >From Rebecca: NM-TRAN 1: $SUBROUTINES ADVAN1 TRANS2; One Compartment Linear Model $PK CL=THETA(1)*EXP(ETA(1)) ; mean clearance V=THETA(2)*EXP(ETA(2)) ; mean central volume K=CL/V ;reparameterization required S1=V $THETA (0,4.) ; clearance estimate (0,10.) ; volume estimate $OMEGA .04 .04 ; twenty percent cv $SIGMA .02 ; ten percent cv $ERROR Y=F+ERR(1) $ESTIMATION MAXEVAL=450 SIGDIGITS=4 $COVARIANCE