re: fast and slow absorption

From MAJ_Ralf_Brueckner@wrsmtp-ccmail.army.mil Thu May 11 09:50:46 1995 Subject: re: fast and slow absorption Many thanks to the NONMEM users who responded to my question regarding modeling fast and slow absorption. In response to Dr. Sheiner's question, here is a representation of what I based my "problem" on. >Before TIME=tka, NONMEM/PREDPP (correctly) calculates predicted drug >amount in COMP 1 (PRED) using rapid KA. But at TIME=tka, >NONMEM/PREDPP suddenly starts calculating PRED as if slow KA had been >used *since time=0*. |* |* A |* + x = DV m | * + + = PRED o | * + * = overlapping u | * + (DV=PRED) n | x x + t | xxx + | xxxx + | xxxxxxx | + xxxxxxx | ++++ | +++++++ ---------------------------------- ^ time | tka Dr. Sheiner and Alison Boeckmann were correct when they suggested that the problem was in the data (I should have known better!). The data was obtained from a rat study using destructive sampling. And as suggested by Alison, >I think that Brueckner's problem may lie partly in his data file. If >he has only event records at time 0 (the dose) and time > tka, the >$PK block computes KA ONLY at time > tka, and so this value of KA is >in effect for the entire integration. That was what had happened. When I reanalyzed the data using the pooled data approach, the "problem" went away and I was able to estimate both KA's. Thanks also to Dr.s Mandema, Grevel and Sheiner for useful models and discussion re: modeling absorption processes. I am most appreciative of this NONMEM Users Network! Ralf Brueckner