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Xpose--an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM.
Model of chemotherapy-induced myelosuppression with parameter consistency across drugs.
- L. Friberg, A. Henningsson, H. Maas, L. Nguyen, M. Karlsson
- Biology, MedicineJournal of clinical oncology : official journal…
- 15 December 2002
A semimechanistic pharmacokinetic-pharmacodynamic model describing chemotherapy-induced myelosuppression through drug-specific parameters and system-related parameters, which are common to all drugs, is proposed and can be a useful tool in the development of anticancer drugs and therapies.
Modeling and Simulation Workbench for NONMEM: Tutorial on Pirana, PsN, and Xpose
This tutorial shows how three commonly used and freely available tools, Pirana, PsN, and Xpose, form a tightly integrated workbench for modeling and simulation with NONMEM.
Prediction-Corrected Visual Predictive Checks for Diagnosing Nonlinear Mixed-Effects Models
The investigated examples demonstrate that pcVPCs have an enhanced ability to diagnose model misspecification especially with respect to random effects models in a range of situations.
Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies
- R. Savic, D. Jonker, T. Kerbusch, M. Karlsson
- Chemistry, MedicineJournal of Pharmacokinetics and Pharmacodynamics
- 26 July 2007
The TRANSIT model is an attractive alternative for modeling drug absorption delay, especially when a LAG model poorly describes the drug absorption phase or is numerically unstable.
Assessment of Actual Significance Levels for Covariate Effects in NONMEM
- U. Wählby, E. Jonsson, M. Karlsson
- MathematicsJournal of Pharmacokinetics and Pharmacodynamics
- 1 June 2001
The objectives of this study were to assess the difference between actual and nominal significance levels, as judged by the likelihood ratio test, for hypothesis tests regarding covariate effects…
Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and Solutions
Empirical Bayes estimates of η- and ε-shrinkage are investigated in pharmacokinetic (PK) pharmacodynamic (PD) modeling, finding their usefulness in the presence of shrinkage is investigated.
Diagnosing Model Diagnostics
Conclusions from clinical trial results that are derived from model‐based analyses rely on the model adequately describing the underlying system and without an understanding of the properties of thesediagnostics, development and use of new diagnostics, and additional information pertaining to the diagnosis, there is risk that adequate models will be rejected and inadequate models accepted.
The importance of modeling interoccasion variability in population pharmacokinetic analyses
Analysis of simulated data with NONMEM shows that ignoring interoccasion variability (IOV) may result in biased population parameter estimates, and supports the simulation findings for the case that IOV is ignored: predictable biases occur in parameter estimates and previously nonexistent period effects are found.
Handling Data Below the Limit of Quantification in Mixed Effect Models
Omission of BQL data was associated with substantial bias in parameter estimates for all tested models even for seemingly small amounts of censored data and an improved standard for VPCs was suggested to better evaluate simulation properties both for data above and below LOQ.