RE: PK data from individuals who vomited after drug ingestion

Dear Kok-Yong Seng, With my naive thinking what happens if you vomit is that a part or all of what is remaining to be absorbed will disappear. If you know the time of vomiting I can see a nice and mechanistic way of handling this. >From your depot compartment you should in this case have an elimination pathway instead of only an absorption pathway. As long as the subject doesn't vomit the elimination pathway is turned off (elimination rate constant=0). If and when a vomiting event is recorded the elimination pathway is turned on for a short and fix amount of time (with the fix amount of time a first order rate constant can conveniently be used to describe this). I have provided a short coding example for this in the end of the email. If you for some reason doesn't have the exact time of the vomiting events I would suggest a covariate for the number of vomiting events within the relevant timeframe (while there is significant absorption). This covariate should then be included for the bioavailability so that the relative bioavailability is 1 for zero vomiting events and relatively different for 1, 2 and 3 vomiting events. This should however in my mind be a far cruder way of handling this than my firs suggestion. ;; Mechanistic vomiting effect on absorption ------------------------- ID AMT TIME DV EVID CMT VOM(vomiting) Comments 1 100 0 . 1 1 0 Dosing 1 . 0.25 0.5 0 2 0 Observation before vomiting 1 . 0.4 . 4 0 0 Vomiting event (obs.VOM=0) 1 . 0.5 . 4 0 1 End of vomiting event (obs.VOM=1) 1 . 0.5 1.25 0 1 0 Observation after vomiting ; In the above described case the vomiting covariate was turned on between TIME 0.4-0.5. $SUBROUTINE ADVAN5 $MODEL COMP = (1_DEPOT) ; Depot compartment COMP = (2_CENT) ; Central observation compartment K1T2 = THETA(1) ; Absorption rate constant (KA) IF(VOM.EQ.1) THEN K1T0 = THETA(2) ; Elimination from depot compartment turned on at vomiting event ELSE K1T0 = 0 ; No elimination from depot compartment without vomiting ENDIF ;; ------------------------------------------------------------------- >From the estimated K1T0 and the fixed time that VOM is set to 1 you can calculate the average fraction of the remaining drug substance in the depot compartment that is lost. I hope that this is of some use to you. Kind regards, Martin Bergstrand, MSc, PhD student ----------------------------------------------- Department of Pharmaceutical Biosciences, Uppsala University ----------------------------------------------- P.O. Box 591 SE-751 24 Uppsala Sweden ----------------------------------------------- [email protected] ----------------------------------------------- Work: +46 18 471 4639 Mobile: +46 709 994 396 Fax: +46 18 471 4003