Re: Modeling of Blood flow data

From:LSheiner Subject:Re: [NMusers] Modeling of Blood flow data Date:Tue, February 19, 2002 6:04 pm Depends on what you mean by "exposure" - rate of absorption does not affect AUC, for example ... > The PK data was modeled using the > following assumptions: 1 compartment linear kinetics with lag time. The > blood flow in this case is measured by laser Doppler and the data are > available at each sampling time point. > > The data set looks as follows: > > ID Time (hrs) DV (ng/ml) Flow > > 1 0 0 2.52 > 1 0.5 0 3.58 > 1 1 0.5 4.58 > 1 2 1.85 2.38 > > etc... > > Can someone help me with suggestions of incorporating the blood-flow > information into the PK model? Seems like a natural for 1st order absorption, as transfer rate (Ka) out of the depot and into the systemic circulation, if it is not diffusion-limited, should be linearly proportional to blood flow to/from the site of absorption. So KA = THETA(1) + THETA(2)*FLOW seems a good place to start. (The FLOW at any given time should be the average flow during the time since the last flow was recorded and the time that this one was recorded; i.e., strictly speaking not the same time as the event record on which it is recorded. If your data require a better approximation to the continuously changing absorption rate, then you'll have to use differential equations and interpolate the flow in $DES) With diffusion limitation, an Emax-type model for flow's effect on KA would be natural. Lag time can be added if need be. _/ _/ _/_/ _/_/_/ _/_/_/ Professor Lewis B Sheiner, MD _/ _/ _/ _/_ _/_/ mail: Box 0626, UCSF, SF, CA,94143 _/ _/ _/ _/ _/ courier: Rm C255, UCSF, SF, CA,94122 _/_/ _/_/ _/_/_/ _/ 415-476-1965 (v), 415-476-2796 (fax)