dose compartment

From: "Vijay V. Upreti" vupre001@umaryland.edu Subject: [NMusers] dose compartment Date: Wed, March 30, 2005 11:35 pm Dear all, I have data from a PK study with small number of subjects, which were given an IV bolus dose followed by IM administration with a washout period in between. I wish to fit this data simultaneously. I have doubt regarding, assigning the dosing compartment for IM administration. I do understand that each NONMEM, PK model has a default dose compartment and CMT can be used in the data item, to specify dosing in any compartment other than default, but I am wondering whether the IM dose should be assigned to the DEPOT or to the PERIPHERAL compartment. Referring to the NONMEM user guide part V, chapter 6, section 8.2.1, page 58, it says an IM injection can be considered as dose to peripheral compartment, I am wondering if one wishes to use a mono exponential decline model like ADVAN2, to fit IM data like this, than by default there is no peripheral compartment. My question specifically is what should be the appropriate compartment for assigning IM dose, depot or peripheral. I have another issue, may be because of delayed sampling time points, I can not see a absorption phase in the IM data and it looks very much similar to IV data, with the first sampling point being Cmax, further the bioavailability > 100 %. In such a case what should be the ideal way to model this data 1. Fix KA based on literature reports or 2. To ignore absorption and model this data just like IV dosing with dose input directly to central compartment. I do not know if this is an appropriate example but in the NONMEM user guide part V, chapter 2, section 3.2, page 13 for a similar situation like this, where time points after oral dosing were delayed and absorption was assumed to be complete, (ADVAN 1) one compartment model, without first order absorption was considered complete. Kindly provide your thoughts, and forgive me for this long email. Thanks in advance. _______________ Vijay V Upreti Graduate Student Pharmacokinetics-Biopharmaceutics Laboratory Department of Pharmaceutical Sciences University of Maryland, School of Pharmacy 20 Penn St., Baltimore, MD 21201 Voice: 410-706-7388 Fax: 410-706-5017