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[NMusers] How to account for M-M in the presence of Ka>Ke constraint in PopPK model

From: Lei Diao <ldiao001_at_umaryland.edu>
Date: Wed, 8 Jul 2015 16:41:04 -0400

Dear NONMEM Users,



I have a popPK model for which the Ka is constrained to be larger than Ke
at the individual level to avoid flip-flop. The question is that if there
is an additional nonlinear clearance component (M-M), how should I
constrain between the absorption rate (KA) and terminal phase elimination
rate (KE) since nonlinear clearance causes the KE to change with time? Is
there any reference on this topic?


KA and KE constraining in the absence of nonlinear clearance in NM code:

KE=((K+K23+K32)-SQRT((K+K23+K32)*(K+K23+K32)-4*K*K32))/2

KA=KE+THETA(5)*EXP(ETA(3))



Thanks a lot for your input!



Lei Diao

Biogen

Received on Wed Jul 08 2015 - 16:41:04 EDT

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