Journal of Pharmacokinetics and Pharmacodynamics
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Individualized optimization of colistin loading doses
Journal of Pharmacokinetics and Pharmacodynamics - Tập 50 - Trang 11-20 - 2022
Colistin remains one of the few available options for the treatment of infections caused by resistant bacteria. Pharmacokinetic (PK) studies have been successful in estimating the appropriate colistin methanesulfonate (CMS) dose to achieve a target colistin concentration. Currently, there is a consensus that the dose of CMS should vary according to the patient renal function since CMS is mainly el......
Estimation of parameters for the elimination of an orally administered test substance with unknown absorption
Journal of Pharmacokinetics and Pharmacodynamics - Tập 40 - Trang 177-187 - 2013
Assessment of the elimination of an oral test dose based on plasma concentration values requires correction for the effect of gastric release and absorption. Irregular uptake processes should be described ‘model independently’, which requires estimation of a large number of absorption parameters. To limit the associated computational effort a new approach is developed with a reduced number of unkn......
From complex data to biological insight: ‘DEKER’ feature selection and network inference
Journal of Pharmacokinetics and Pharmacodynamics - Tập 49 - Trang 81-99 - 2021
Network inference is a valuable approach for gaining mechanistic insight from high-dimensional biological data. Existing methods for network inference focus on ranking all possible relations (edges) among all measured quantities such as genes, proteins, metabolites (features) observed, which yields a dense network that is challenging to interpret. Identifying a sparse, interpretable network using ......
Generative models for age, race/ethnicity, and disease state dependence of physiological determinants of drug dosing
Journal of Pharmacokinetics and Pharmacodynamics - Tập 50 - Trang 111-122 - 2022
Dosing requires consideration of diverse patient-specific factors affecting drug pharmacokinetics and pharmacodynamics. The available pharmacometric methods have limited capacity for modeling the inter-relationships and patterns of variability among physiological determinants of drug dosing (PDODD). To investigate whether generative adversarial networks (GANs) can learn a generative model from rea......
Constant infusion case of one compartment pharmacokinetic model with simultaneous first-order and Michaelis–Menten elimination: analytical solution and drug exposure formula
Journal of Pharmacokinetics and Pharmacodynamics - Tập 48 - Trang 495-508 - 2021
The main objective of this article is to propose the closed-form solution of one-compartment pharmacokinetic model with simultaneous first-order and Michaelis–Menten elimination for the case of constant infusion. For the case of bolus administration, we have previously established a closed-form solution of the model through introducing a transcendent X function. In the same vein, we found here a c......
Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis
Journal of Pharmacokinetics and Pharmacodynamics - Tập 43 - Trang 45-54 - 2015
Improving the quality of exposure–response modeling is important in clinical drug development. The general joint modeling of multiple endpoints is made possible in part by recent progress on the latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate, when modeling a continuous and a categorical clinical endpoint, the level of improve......
Survey of monoclonal antibody disposition in man utilizing a minimal physiologically-based pharmacokinetic model
Journal of Pharmacokinetics and Pharmacodynamics - Tập 41 - Trang 571-580 - 2014
Minimal physiologically based pharmacokinetic (mPBPK) models provide a simple and sensible approach that incorporates physiological elements into pharmacokinetic (PK) analysis when only plasma data are available. With this modeling concept, a second-generation mPBPK model was further developed with specific accommodations for the unique PK properties of monoclonal antibodies (mAb). This study appl......
Computational pharmacokinetics/pharmacodynamics of rifampin in a mouse tuberculosis infection model
Journal of Pharmacokinetics and Pharmacodynamics - Tập 42 - Trang 375-389 - 2015
One critical approach to preclinical evaluation of anti-tuberculosis (anti-TB) drugs is the study of correlations between drug exposure and efficacy in animal TB infection models. While such pharmacokinetic/pharmacodynamic (PK/PD) studies are useful for the identification of optimal clinical dosing regimens, they are resource intensive and are not routinely performed. A mathematical model capable ......
A Bayesian approach for the estimation of patient compliance based on the last sampling information
Journal of Pharmacokinetics and Pharmacodynamics - - 2011
Exponential tails of drug disposition curves: Reality or appearance?
Journal of Pharmacokinetics and Pharmacodynamics - Tập 41 - Trang 49-54 - 2013
Since plasma drug concentration–time curves, C(t), can be examined only over a limited time range, it is unclear whether they have an exponential or power-law tail. An answer to this question is important because of the necessary extrapolation beyond the observation period (to infinity). Based on renewal theory, the present analysis shows that due to the recirculation process drug disposition curv......
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