Evaluation of Methods for Estimating Time to Steady State with Examples from Phase 1 Studies
Journal Title: The AAPS Journal - Year 2008, Vol 10, Issue 1
Abstract
An overview is provided of the methodologies used in determining the time to steady state for Phase 1 multiple dose studies. These methods include NOSTASOT (no-statistical-significance-of-trend), Helmert contrasts, spline (quadratic) regression, effective half life for accumulation, nonlinear mixed effects modeling, and Bayesian approach using Markov Chain Monte Carlo (MCMC) methods. For each methodology we describe its advantages and disadvantages. The first two methods do not require any distributional assumptions for the pharmacokinetic (PK) parameters and are limited to average assessment of steady state. Also spline regression which provides both average and individual assessment of time to steady state does not require any distributional assumptions for the PK parameters. On the other hand, nonlinear mixed effects modeling and Bayesian hierarchical modeling which allow for the estimation of both population and subject-specific estimates of time to steady state do require distributional assumptions on PK parameters. The current investigation presents eight case studies for which the time to steady state was assessed using the above mentioned methodologies. The time to steady state estimates obtained from nonlinear mixed effects modeling, Bayesian hierarchal approach, effective half life, and spline regression were generally similar.
Authors and Affiliations
Lata Maganti, Deborah L. Panebianco, Andrea L. Maes
Keywords
Related Articles
- EP ID EP681523
- DOI 10.1208/s12248-008-9014-y
- Views 83
- Downloads 0
Comparative evaluation of tableting compression behaviors by methods of internal and external lubricant addition: Inhibition of enzymatic activity of trypsin preparation by using external lubricant addition during the tableting compression process
This study evaluated tableting compression by using internal and external lubricant addition. The effect of lubricant addition on the enzymatic activity of trypsin, which was used as a model drug during the tableting com...
Addressing the Challenges of Low Clearance in Drug Research
As a result of high-throughput ADME screening, early metabolite identification, and exploration of novel chemical entities, low-intrinsic-clearance compounds continue to increase in drug discovery portfolios. Currently a...
Fish pharmacokinetics database updated
Interactions of Everolimus and Sorafenib in Pancreatic Cancer Cells
Everolimus targets the mammalian target of rapamycin, a kinase that promotes cell growth and proliferation in pancreatic cancer. Sorafenib inhibits the Raf-mitogen-activated protein kinase, vascular endothelial growth fa...
Antidrug Antibody Assay Validation: Industry Survey Results
Immunogenicity of biopharmaceutical products has attracted considerable attention from the industrial, academia, and regulatory organizations. Many methods exist to detect and characterize level of antidrug antibody resp...