Re: Cl/F and V/F

From:Nick Holford Subject:Re: [NMusers] Cl/F and V/F DateTue, 30 Jul 2002 09:42:15 +1200 Paul, I think you are making things more complicated than they really are. The post hoc estimates of CL and V are NOT CL/F1 and V/F1. The CL, V and F1 parameters are separately estimated. However, the values of CL and V are obtained under the assumption that F1 for formulation 0 is 1. This assumption may be wrong but no harm comes to the modelling by assuming it. I note that you do not allow any between subject variability in F1 in your code. I can see no reason not to include this in the model. I would consider using: F1=TVF1*EXP(ETA(F1)) This may be more important than including BSV on CL. Your rats may be essentially clones and BSV on CL and V may be quite small but F1 depends on other factors (e.g. the formulation variability). This could account for more rat to rat variation in the concs than disposition parameters. Remember that the usual SHAM methods for bioequivalence make the assumption that CL is identical and formulation differences in AUC are due only to differences in F1. Nick