Multiple dose analysis using NONMEM

From: "Vipul Gupta" vipul686@gmail.com Subject: [NMusers] Multiple dose analysis using NONMEM Date: Mon, 10 Jul 2006 00:40:55 -0400 Hi All, I am trying to analyze a multiple dose oral PK data using NONMEM. The drug is given on 12 h dosing interval for over 30-40 weeks. There are 10-12 sampling points available in first 24 h and then one peak and one trough sample is available until the last dose. Following last dose, 10-12 data points are available for next 24 h. A comparison of first and last dose PK profile indicates a one compartment model with decrease in Cl. The drug is known to cause auto inhibition of its metabolism over time. Data is available only for the parent drug and no information on F is available. My question is : I am not aware of how the changing clearance with time can be modelled using NONMEM ? Any inputs will be appreciated. Thank you Sincerely, Vipul Kumar Post Doc Fellow Department of Pharmaceutics Univ of Florida, Gainesville.