problem with acquiring post hoc estimates

From: Kristel Crommentuyn, pharmD Apkcr@SLZ.NL Subject: [NMusers] problem with acquiring post hoc estimates Date: Tue, May 18, 2004 11:21 am Dear all, We are experiencing problems with a pk model, in acquiring post hoc estimates and hope someone will be able to help us The model describes the pharmacokinetics of an orally dosed compound and its metabolite in children. The data consists of complete pharmacokinetic curves as well as sparse samples for 38 subjects at different occasions (1-28). Both parent and metabolite data are best described with a one-compartment model with first-order elimination. Cl and V are allometrically scaled for body weight. The frequency of administration is a covariate on Cl1. We would like to generate posthoc estimates for the Cmin of the parent compound and metabolite to use in a pharmacodynamic analysis. When we use the controlstream (below) and dataset (enclosed test1.csv) the Cmin posthocs for both compounds are equal, whereas at the other time-points they differ. $PK TVCL1=THETA(1)*THETA(6)**FREQ CL1=TVCL1*(WT/18)**0.75*EXP(ETA(1)) TVV1=THETA(2)*(WT/18)**1.0 V1=TVV1*EXP(ETA(2)) K12=CL1/V1 D1=THETA(3)*EXP(ETA(3)) TVCL2=THETA(4)*(WT/18)**0.75 CL2=TVCL2*EXP(ETA(4)) TVV2=THETA(5)*(WT/18)**1.0 V2=TVV2*EXP(ETA(5)) K20=CL2/V2 F1=1*EXP(VF) S1=V1 S2=V2 I hope that someone can help us with this. Best regards, Kristel ___________________________________ Kristel Crommentuyn, pharmD AIDS research pharmacist Department of Pharmacy and Pharmacology Slotervaart Hospital Louwesweg 6 1066 EC Amsterdam The Netherlands apkcr@slz.nl 020-5124737