Re: Modeling of Blood flow data

From: Nick Holford Subject: Re: [NMusers] Modeling of Blood flow data Date: Tue, February 19, 2002 5:50 pm Partha, Its hard to tell from the fragment of data if there is much information in blood flow about the absorption process (When does the conc peak?). However, the data looks rather sparse and so I would guess you can only hope to learn a little bit. I would start out using a simple empirical model in ADVAN2 eg. KA = POPKA * EXP(KFLOW*FLOW) This will increase absorption rate as FLOW increases when KFLOW>0. This model has the useful property that it cannot predict negative values of KA and if KFLOW is "small" then it approximates the linear function: KA = POPKA * (1 + SLOPE*FLOW) This linear form is usually easier to explain to your pharmacometrically challenged clinical colleagues. If you can detect an improvement in the fit then you could make the model more sophisticated by using a DE defined model and having KA vary continuously with FLOW by using a linear interpolation between the observed flow values during the times between the observations. There are more physiologically based representations of drug absorption across the skin involving various skin compartments, permeability factors and blood flow but I doubt if your data can identify the various components involved. I note you say that "the rate of absorption and hence the systemic exposure to the drug is dependent on the blood flow at the site of administration". If you are thinking of extent of absorption when you say systemic exposure I would point out that the model I have proposed above would not be expected to change extent. Changing the rate of absorption does not change extent of absorption unless you have a more complex model with rate dependent extraction of drug before it reaches the systemic circulation. Nick Nick Holford, Divn Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/