SAAM Institute

WinNonlin, Pharsight Corp., http //www.pharsight.com SAAM II, SAAM Institute, Inc., http //www.saam.com TOXICOKINETIC SOFTWARE... 

SAAM II User guide. Seattle, WA SAAM Institute 1998. 

Atkinson AJ Jr. Gentamicin kinetics A simulation case study. In Foster DM, Atkinson AJ Jr. Principles of pharmacokinetic data analysis Modeling and simulation (workshop manual). Seattle SAAM Institute, Inc. 2004. 

This ability is available in many software programs. NONMEM (Iconus, EUicott City, MD) has been widely used to estimate population models arising from both sparse and intensely sampled data. Other programs include WinNonMix (Pharsight Corp., Palo Alto, CA), Kinetica 2000 (Innaphase Corp, Philadelphia, PA), and Pop-Kinetics (SAAM Institute, Seattle, WA). ADAPT II and WinNonlin have focused on PK/PD models and have been combined with Bayesian approaches to estimate population models. 

The AIC used by Yamaoka et al. is not the exact AIC reported by Akaike but is slightly different. However, its use is valid if all the models under consideration all have the same log-likelihood function. Yamaoka et al. (1978) demonstrated the use of the AIC by distinguishing between mono-exponential, bi-exponential, and tri-exponential equations. However, not all software packages use this definition. For example, WinNonlin (Pharsight Corp., Cary NC) uses Eq. (1.45) with p equal to only the number of structural model parameters and does not include the estimated residual variance. SAAM II (SAAM Institute, Seattle, WA) calculates the AIC as... 

Hence, intravenous data were modeled first, followed by inhalational, then intranasal. Once the pharmacokinetics of each individual route of administration was established, all model parameters were then estimated simultaneously. Initial values for cocaine pharmacokinetics after intravenous administration were estimated using noncompartmental methods. Total systemic clearance was estimated at 100 L/h and volume of distribution at steady-state was estimated at 232 L. Central compartment clearance and intercompartmental clearance were set equal to one-half total systemic clearance (50 L/h), whereas central and peripheral compartment volumes were set equal to one-half volume of distribution (116 L). Data were weighed using a constant coefficient of variation error model based on model-predicted plasma concentrations. All models were fit using SAAM II (SAAM Institute, Seattle, WA). An Information-Theoretic approach was used for model selection, i.e., model selection was based on the AIC. 

FIG. 5. Preliminary model to lit appearance of label frompyridoxal, pyridoxine, and pyridox-amine in urine as pyridoxic add (Figure produced by SAAM II from the SAAM Institute, University of Washington, Seattle, WA 98195.)... 

SAAM 11 User Guide 1998. SAAM Institute FL-20, University of Washington, Seattle, WA. 

Lei Jong and John C Saam Michigan Molecular Institute, Midland, MI 48<40-2< 96... 

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