Talk:Plateau principle

Drafting

This article is under construction. When fully developed, it will include examples from nutrition, pharmacology, and biological system dynamics. Jhargrov (talk) 17:24, 7 October 2009 (UTC)James HargroveJhargrov (talk) 17:24, 7 October 2009 (UTC)

I have now finished developing the basic concepts for the Plateau Principle. The article is ready for review and general use by others. Jhargrov (talk) 14:48, 9 October 2009 (UTC)James HargroveJhargrov (talk) 14:48, 9 October 2009 (UTC)

Request for review of Plateau Principle

It would be very helpful to obtain an expert review of this new entry. Requests have been made on the System Dynamics page and the Pharmacokinetics page. Please delete this section when a review has been done. Many thanks. Jhargrov (talk) 14:03, 10 October 2009 (UTC)

In the general context of a variable drug volume in time, the first order assumption does not imply any specific functional shape, especially not an exponential or sum of exponential terms (SET). SETs are perhaps best understood as applying to an instant-mixing, constant-volume-compartmental approach. However, that approach is rather unrealistic, and does not work very well for predicting multi-dosing. In specific, as relates to multi-dosing or constant infusion, from compartmental modeling of a bolus intravenous dosage, there is no reliable prediction of a plateau concentration. For constant infusion, the instant-mixing assumption becomes irrelevant as there is zero drug in the body at the initial infusion start time. The only way to get a single dose model to agree with constant infusion and multi-dosing is to remove the bolus-model, instant-mixing assumption, and the only way to do that is by defining drug volume of distribution to be that volume that contains drug at any specific time and then requiring the initial volume of drug distribution to be zero. SET functions cannot achieve zero initial volume when used as washout functions, i.e., having positive coefficients. However, under certain circumstances a gamma distribution can have the required properties of zero volume at time is zero. When applied to the gamma variate model as obtained using adaptive Tikhonov regularization, this should enormously simplify the plateau calculations and the multiple confusing assorted definitions of half-lives used for multiple dosing . Suggest reading with particular attention to the relationship between bolus intravenous washout models and constant infusion on bottom of page 3/16 and top of page 4/16. Note there is a typo and "Once we have a p(t), its derivative is p(t)" should read "Once we have a P(t), its derivative is p(t)." Please contact the corresponding author, i.e., me, for any discussion. Also note, I will not propose any change to this Wikipedia entry unless the other contributors to this entry are in agreement.CarlWesolowski (talk) 18:07, 5 August 2016 (UTC)

References