saturable first-pass metabolism

From: "andy lie" zhenqung@yahoo.com Subject: [NMusers] saturable first-pass metabolism Date: Mon, October 4, 2004 10:32 pm All, I have a set of oral data that showed increase bioavailability with increasing dose and it follows a biphasic disposition with similar terminal half lives across different doses. However, I don't have IV data. Is that still a way to look at the change of F as a function of Dose in the 2-cmp model and can someone tell me the codes if possible??? Thanks. ZhenQung

From: "Nick Holford" Subject: RE: [NMusers] saturable first-pass metabolism Date: Tue, October 5, 2004 2:40 am Andy, Try the following. It empirically models an increase of F1 with dose using an exponential function. It also describes the random between subject variability in F1. You can play around with the empirical model to see if you can do better than the exponential. If you have more than one dosing occasion in each subject then looking for between occasion variability in F1 is a good idea too. $THETA .01; kf1 $OMEGA .5 ; etaf1 $PK ... IF (NEWIND.LE.1) THEN DOSE=0 DOSSTD=1 ; change this to the median or most commonly studied dose ENDIF IF (AMT.GT.0) DOSE=AMT ... F1=EXP(THETA(kf1)*(DOSE-DOSSTD))*EXP(ETA(etaf1)) Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ _______________________________________________________