Non-zero concentrations at zero time

Dear Group, I am working on a data set with PK -PD assessments from a three way cross-over study with different formulations of the drug. I have measurable concentrations at Time zero right from period 1 and the analyte of interest can come from food. I appreciate your ideas on handling this situation. Regards, Ayyappa

Dear Ayyappa, You can initialize the concentration of your compartments using the command, e.g. A_0(1)=XX. The initialization amount can be a number or can be modelled as a model parameter with THETAs and ETAs. An overview of baseline initialization methods (with NONMEM code examples in appendix) can be found here: Dansirikul C, Silber HE, Karlsson MO. Approaches to handling pharmacodynamic baseline responses. Journal of pharmacokinetics and pharmacodynamics 35: 269-83, 2008. http://www.ncbi.nlm.nih.gov/pubmed/18446428 In your case, if you suspect that the analyte is there both because of food and due to an insufficient wash-out period, you could put in your dataset all the doses (also from previous periods) and then add an extra dummy dose just before your baseline observations. You could use the bioavailability of that dummy dose as an extra parameter to estimate, which would correct for the difference between what is expected to be still there from previous doses (if any) and what comes from other sources (food). I hope this helps. Regards from Cape Town, Paolo