Hi Khaled, Previously Mats Karlsson suggested a model for autoinduction for a compound using a hypothetical enzyme compartment. I have used that for various types of dosing regimens. You could adapt this into autoinhibition of metabolite formation.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&Te rmToSearch=10594468&ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubm ed_ResultsPanel.Pubmed_RVDocSum http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&Te rmToSearch=10848719&ordinalpos=6&itool=EntrezSystem2.PEntrez.Pubmed.Pubm ed_ResultsPanel.Pubmed_RVDocSum Plotting A(1), A(2) and A(3) will show how these compartments work. The enzyme compartment needs to be initialized with an AMT of 1 in the dataset for each ID. I have suggested some code below for 1-comp parent, 1-comp metabolite without absorption and complete transformation from parent to metabolite. No doubt you can expand this to your desired 2-comp model. $SUBROUTINES ADVAN6 TOL=3 $MODEL COMP=(CENTRAL) COMP=(ENZ) COMP=(METAB) $DES CM=A(3)/V3 DADT(1)=-(K13*A(2))*A(1) ;;parent conc DADT(2)=KENZ-KENZ*A(2)*(1+(CM/(CM+IC50))) ;; hypothetical enzyme DADT(3)=K13*A(1)-K30*A(3) ;; metabolite conc With friendly regards, Thomas Thomas Kerbusch, PhD Section Head PK-PD Dept. CPK N.V. Organon - XW 3133 PO Box 20 5340 BH Oss The Netherlands tel: +31 412 661621 cell: +31 613045046 (intern 4936) fax: +31 412 662542 [EMAIL PROTECTED] -----Original Message----- From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of Khaled Mohammed Abduljalil Sent: Friday, 22 June, 2007 12:50 To: [email protected] Subject: [NMusers] autoinhibition Dear nmusers, Could anyone support me with nonmem code for a drug undergoes in vivo hepatic metabolism leading to formation of a metabolite. This metabolite has the ability to inactivate parent drug transformation. Both parent and metabolite data can be fitted with a single model of two-compartment. thanks in advance khaled This message, including attachments, is confidential and may be privileged. If you are not an intended recipient, please notify the sender then delete and destroy the original message and all copies. You should not copy, forward and/or disclose this message, in whole or in part, without permission of the sender.
