Hi, I have a question about the deconvolution module (not IVIVC) in winnonlin. I am trying to deconvolve a formulation’s plasma profile. I fitted an IR profile adequately with a one-compartment with lagtime model and obtained the parameters K01, K10, V_F. When I switched to the deconvolution module, the program prompted me to input the Exponential Term Estimates A1 and Alpha1. What are these exponental terms? Thanks. John
Hi John, The Exponential Term Estimates A1 and Alpha1 are the intercept and slope that will be used to perform the numerical deconvolution and they equate to Czero and K10 in a 1 com model after IV bolus dosing. So you have to do one more step, simulate your data with the same Dose, V and K10 as before but with an IV model. Then you can read Czero form the Predicted data tab, don’t forget that a) this is assuming 100% Bioavailability and b) you should dose normalise the intercept to be sure your Fabs in deconvolution is correct Simon.
Hi Simon, Thank you. One question, what do you mean by “dose normalize the intercept to be sure your Fabs in deconvoluton is correct”? John sdavis wrote: [quote]Hi John, The Exponential Term Estimates A1 and Alpha1 are the intercept and slope that will be used to perform the numerical deconvolution and they equate to Czero and K10 in a 1 com model after IV bolus dosing. So you have to do one more step, simulate your data with the same Dose, V and K10 as before but with an IV model. Then you can read Czero form the Predicted data tab, don’t forget that a) this is assuming 100% Bioavailability and b) you should dose normalise the intercept to be sure your Fabs in deconvolution is correct Simon.[/quote]
John, imagine you had some Oral tablet of 20mg, if normalise this to 1mg then you would expect Czero to be one-twentieth - this is the UIR or Unit Impulse Response you may see in some of the manuals. If you use this as the “A” then when you enter other dose amounts e.g. 15mg for other formulations then the scaling to get the correct Fabs is done for you, rather than you having to calculate the ratio each time. Is that clearer? Simon. (PS it’s only necessary to quote the part of the text you want me to comment on, not the whole message - then we can keep the threads easier to review and index)
Got it. Thanks Simon