ADVAN6 coding question

From: "Garry Boswell" gboswell@tanox.com Subject: [NMusers] ADVAN6 coding question Date: Fri, 24 Mar 2006 17:17:09 -0600 NMUsers, I would like to ask the group for some help. I would like to know how to write the NONMEM code for a particular model. In a publication by Bauer et al (J Pharmacokinetics and Biopharmaceutics 27(4), 1999. 397:420) the authors propose a PK/PD model that is equivalent to an indirect response model. The model is a 2 compartment model with first order and MM elimination from the central compartment. Their Model B has the following differential equations: A = amount compound A B = amount CD11a cells dA1/dt = -(k12+k10)*[A1]-Vm*[A1}*[B]/(Km+[A1]) + k21*[A2] + Dose_rate dA2/dt = k12*[A1] - k21*[A2] dB/dt = k03 k30*[B] Vm2*[A1}*[B]/(Km+[A1]) the $DES block should be similar to this (for an IV bolus dose): $DES DADT(1) = -(K10+K12)*A(1) +K21*A(2) -(VM*A(1)*B)/(KM+A(1)) DADT(2) = K12*A(1) -K21*A(2) D??DT = K03 - B*K30 -(VM2*A(1)*B)/(KM+A(1)) Additionally, in previous posting to this group the comment has been made that the Effect compartment needs to be initialized with a dummy AMT = 1 at t=0 for indirect models. Would this also apply to the above case where the measurement in the Effect compartment is not of Compound A but of the number of CD11a cells? TIA Garry