RE: Modeling of iv and po data

From: Nick Holford n.holford@auckland.ac.nz Subject: RE:[NMusers] Modeling of iv and po data Date: Wed, August 11, 2004 4:54 pm Toufigh, If you have mixed order elimination detectable from the IV dose then it is quite possible that you will have rate dependent first pass extraction with the oral dose e.g. see Holford NHG. Complex PK/PD models - an alcoholic experience. International Journal of Clinical Pharmacology and Therapeutics 1997;35(10):465-468. I would not worry about lack of convergence until you have got a good handle on the structural model. In the end the visual goodness of fit of the observed and predicted values and perhap a simple predictive check (simulation from your final model) are more meaningful than NONMEM's semi-arbitrary decision to declare 'convergence'. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/ _______________________________________________________