Hi, all friends I am working on building a oral model with "Generic SimBiology PBPK model" and meet some problems about intestinal transit rate. Take duodenum as example, the transit rate is defined as " _(kTransportSmallIntestine*organismLengthDuodenum/organismLengthSmallInstestine)*Duodenum.DrugDissolved_". I think assuming duodenum transit time is equal to _SmallIntestineTransittime*organismLengthDuodenum/organismLengthSmallInstestine_, the transit rate constant is the inverse of that,which result in _kTransportSmallIntestine*organismLengthSmallInstestine/organismLengthDuodenum_, contradicting with the equation in model. Am I wrong? Besides that, the _kTransportSmallIntestine_is defined as _0.693/organismMeanResidenceSmallIntestine_ in model. Isn't the mean residence time determining the time at which about 63.2% of initial amount having passed through the compartment and inverse of mean residence time determining the transit rate? Why does _organismMeanResidenceSmallIntestine_ correlate with 0.693 which is often seen in half-life associated expression? Thanks for any comment. Questions on intestinal transit rate in "Generic SimBiology PBPK model" Let me look into this and get back to you! Hi Wei Wang, Sorry it took some time to get back to you. We needed some time to get to the bottom of this. * I agree with you that implementation of the transit time is incorrect. * The original paper (Sheila Peters, 2008) uses a Kt_i = 0.035, for each of the seven compartments, which corresponds to a transit time of 28.57 minutes for each compartment * This is consistent with a Kt_total = 0.005 for the entire small intestine, which corresponds to a total transit time of 200 minutes (200/7 = 28.57), which is consistent with a publication I found * The SimBiology implementation normalizes the transit time for each compartment by using the length of each compartment, _length_segmenti_. * If we assume _T_i = T_total*length_segmenti/length_total_ * Then _Kt_i = 1/T_i = 1/T_total * length_total/length_segmenti = Kt_total* length_total/length_segmenti_ * And we can check that _T_total = Sum (T_i) = 1/Kt_total * Sum(length_segmenti)/length_total = 1/Kt_total * 1_ * Thus, Changing _Kt_i = Kt_total*length_segment/length_total_ to _Kt_i = Kt_total *length_total/length_segment_ solves the problem: Regarding your second question, we are not sure where the factor 0.693 comes from. If you look at Sheila Peters’ paper, the small intestine transit rate Kt = 0.035 in humans, see table 1. As I explained above, this is consistent with a transit time of 200 minutes or 3 1/3 hr. In the Simbiology model * The parameter _Kt_total_ is called _kTransportSmallIntestine_ * With an initial assignment on _kTransportSmallIntestine = 0.693/organismMeanResidenceSmallIntestine_ * _organismMeanResidenceSmallIntestine = 3.33 hours_ (200 minutes, see Yu and Amidon 1998). * If we want to be consistent with the Peters’ paper, I think the factor 0.693 should change to 1 to result in _kTransportSmallIntestine = 1 /organismMeanResidenceSmallIntestine_ Sorry for the inconvenience and thanks for your message! We will update the FileExchange entry with these changes. # Peters, S. A. (2008). Evaluation of a generic physiologically based pharmacokinetic model for lineshape analysis. Clinical pharmacokinetics, 47(4), 261-75. # Yu, L.X. and Amidon, G.L. (1998). Characterization of small intestinal transit time distribution in humans. International Journal of Pharmaceutics, 171, 157-163. Hi, Sietse Braakman , Thanks for your reply and it's really helpful. So where may I find the FileExchange entry in the future? In the same place: <https://www.mathworks.com/matlabcentral/fileexchange/37752-generic-simbiology-physiologically-based-pharmacokinetic-pbpk-model link to entry> We will change the version number from 1.2.0.0 to 1.2.1.0 once it is updated. I have now updated the model on the FileExchange. Thanks for your concern a lot. pbpk transit rate
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