analysis of non-positive DV

Dear NONMEM users, I'm analyzing a dataset of 4 patients, there are 2 types of observations for each patient - vehicle (say baseline) and dose (treatment). We want to analyze our dataset in terms of (treatment-baseline). So I've modified my dataset, and now I have only one "column" of observations for each patient: DV= (treatment-baseline). But now I have some problems because I have some negitive values in DV column. In case of some models it results in problems, for example: TEFF = TBAS + (TSLP*CP)**TALP so TSLP should be positive but it's not that right... Maybe there are some common methods to deal with this case? Thanks a lot, Svetlana