From: "Ritu Lal" Ritu.Lal@XenoPort.com Subject: [NMusers] FW: question for absorption modeling Date: Fri, 4 Nov 2005 08:41:54 -0800 Dear NM users, I am trying the following models for modeling the absorption phase of my compound. This is data for a drug administered orally. Currently, I am using ADVAN2 (one compt. oral absorption model with first order absorption and lag time), but there is some model misspecification in the absorption phase. These are the 2 other models I would like to try: 1. sequential first and zero-order abn with lag time, one compt model 2. only zero order absorption with lag time, one cpmpt model How do I set up my data file (how do I enter RATE for the zero-order absorption?) and control file for these 2 situations? Can I continue using the library models or do I need to switch to user written subroutines? Thanks, Ritu Ritu Lal, Ph.D. Sr. Director, Pharmacokinetics and Drug Metabolism Xenoport 3410 Central Expressway Santa Clara, CA 95051 Phone (408)616-7199 Cell (408)483-3741 Fax (408)616-7212 e-mail ritu.lal@xenoport.com _______________________________________________________ From: Justin Wilkins justin.wilkins@farmbio.uu.se Subject: Re: [NMusers] question for absorption modeling Date: Mon, 07 Nov 2005 10:42:58 +0100 Hi there, I don't think there'll be any problem using the library routines for this. Specifying RATE=-2 indicates that the durations (as opposed to rates) of zero-order bolus doses will be calculated by PK. For ADVAN2/TRANS2 you might use a data file structure similar to the following example: #ID RATE TIME DV MDV AMT EVID 1 -2 0 0 1 600 1 1 0 1.55 3.98 0 0 0 1 0 3.13 4.32 0 0 0 1 0 4.78 3.22 0 0 0 2 -2 0 0 1 600 1 2 0 3.18 0.55 0 0 0 2 0 4.48 3.62 0 0 0 ... and so on. You would specify the D1 (duration of zero order infusion) parameter in the model specification file, similarly to the below (while retaining KA): TVCL = THETA(1) ; CL CL = TVCL*EXP(ETA(1)) ; CL TVV = THETA(2) ; V2 V = TVV*EXP(ETA(2)) ; V2 TVKA = THETA(3) ; KA KA = TVKA*EXP(ETA(3)) ; KA TVD1 = THETA(4) ; D1 D1 = TVD1*EXP(ETA(4)) ; D1 Another option to consider when dealing with awkward absorption and associated lag times might be the transit compartment model - it's still in manuscript but a broad outline was presented at PAGE 2004: PAGE 13 (2004) Abstr 513 [www.page-meeting.org/?abstract=513] Best regards Justin _______________________________________________________