Journal ArticleDOI
Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies
Radojka M. Savic,Daniël M. Jonker,Daniël M. Jonker,Thomas Kerbusch,Thomas Kerbusch,Mats O. Karlsson +5 more
TLDR
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.Abstract:
Purpose: To compare the performance of the standard lag time model (LAG model) with the performance of an analytical solution of the transit compartment model (TRANSIT model) in the evaluation of four pharmacokinetic studies with four different compounds. Methods: The population pharmacokinetic analyses were performed using NONMEM on concentration–time data of glibenclamide, furosemide, amiloride, and moxonidine. In the TRANSIT model, the optimal number of transit compartments was estimated from the data. This was based on an analytical solution for the change in drug concentration arising from a series of transit compartments with the same first-order transfer rate between each compartment. Goodness-of-fit was assessed by the decrease in objective function value (OFV) and by inspection of diagnostic graphs. Results: With the TRANSIT model, the OFV was significantly lower and the goodness-of-fit was markedly improved in the absorption phase compared with the LAG model for all drugs. The parameter estimates related to the absorption differed between the two models while the estimates of the pharmacokinetic disposition parameters were similar. Conclusion: Based on these results, 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.read more
Citations
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Journal ArticleDOI
Basic concepts in population modeling, simulation, and model-based drug development-part 2: introduction to pharmacokinetic modeling methods.
TL;DR: This paper is the second in a three‐part series, providing an introduction into methods for developing and evaluating population pharmacokinetic models, and example model files are available in the Supplementary Data online.
Journal ArticleDOI
Importance of Shrinkage in Empirical Bayes Estimates for Diagnostics: Problems and Solutions
TL;DR: 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.
Journal ArticleDOI
Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy : Second Consensus Report
Mercè Brunet,Teun van Gelder,Anders Åsberg,Vincent Haufroid,Vincent Haufroid,Dennis A. Hesselink,Loralie J. Langman,Florian Lemaitre,Pierre Marquet,Christoph Seger,Maria Shipkova,Alexander A. Vinks,Alexander A. Vinks,Pierre Wallemacq,Eberhard Wieland,Jean-Baptiste Woillard,Markus J. Barten,Klemens Budde,Helena Colom,Maja Theresa Dieterlen,Laure Elens,Kamisha L. Johnson-Davis,Paweł K. Kunicki,Iain MacPhee,Satohiro Masuda,Binu S. Mathew,Olga Millán,Tomoyuki Mizuno,Tomoyuki Mizuno,Dirk Jan A.R. Moes,Caroline Monchaud,Ofelia Noceti,Tomasz Pawinski,Nicolas Picard,Ron H.N. van Schaik,Claudia Sommerer,Nils Tore Vethe,Brenda C. M. de Winter,Uwe Christians,Stein Bergan +39 more
TL;DR: It is concluded that considerable advances in the different fields of tacrolimus monitoring have been achieved during this last decade, and the Expert Committee concludes that Continued efforts should focus on the opportunities to implement in clinical routine the combination of new standardized PK approaches with PG, and valid biomarkers to further personalize tacolimus therapy and to improve long-term outcomes for treated patients.
Journal ArticleDOI
Pharmacokinetic Evaluation of the Penetration of Antituberculosis Agents in Rabbit Pulmonary Lesions
Maria C. Kjellsson,Maria C. Kjellsson,Laura E. Via,Anne Goh,Danielle M. Weiner,Kang Min Low,Steven E. Kern,Goonaseelan Pillai,Clifton E. Barry,Véronique Dartois +9 more
TL;DR: Though further refinement is needed to accurately predict the behavior of these drugs in human subjects, the results enable the integration of lesion-specific pharmacokinetic-pharmacodynamic (PK-PD) indices in clinical trial simulations and in in vitro PK-PD studies with M. tuberculosis.
Journal ArticleDOI
Food, gastrointestinal pH, and models of oral drug absorption
TL;DR: Understanding of the physicochemical and physiological rate‐limiting factors affecting oral absorption, modellers can implement simplified population‐based modelling approaches that are less complex than whole‐body physiologically‐based models but still capture the essential elements in a physiological way and hence will be more suited for population modelling of large clinical data sets.
References
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Malcolm Rowland,Thomas N. Tozer +1 more
TL;DR: The Third Edition of Clinical Pharmacokinetics features considerations of both stereochemistry and the increasing number of polypeptide and protein drugs being developed.
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Xpose--an S-PLUS based population pharmacokinetic/pharmacodynamic model building aid for NONMEM.
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TL;DR: Xpose is presented, a model building aid for population PK/PD analysis using NONMEM, which simplifies the task of producing documentation, data set checkout plots, goodness of fit plots and graphical model comparison.
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