Pharmacokinetic-dynamic

Sheiner LB, Ludden TM. Population pharmacokinetics/dynamics. Annu Rev Pharmacol Toxicol 1992 32 185-209. 

Pfizer Global Research Development Pharmacokinetics, Dynamics and Metabolism... 

Axelson, D., Perel, J., Rudolph, G., Birmaher, B., Nuss, S., and Brent, D. (2000b) Significant differences in pharmacokinetics/dynamics... 

Pfizer Global Research and Development, Department of Pharmacokinetics, Dynamics ... 

Ayman El-Kattan, Senior Principal Scientist, Pfizer Global Research and Development, Department of Pharmacokinetics, Dynamics and Metabolism, Groton, CT... 

Yunsheng Hsieh, Senior Principal Scientist, Schering-Plough Research Institute, Department of Drug Metabolism and Pharmacokinetics, Kenilworth, NJ John Janiszewski, Associate Research Fellow, Pfizer Global Research and Development, Department of Pharmacokinetics, Dynamics and Metabolism, Groton, CT Elliott B. Jones, Senior LC-MS Laboratory Manager, Applied Biosystems, Foster City, CA... 

The pharmacokinetic/dynamic parameters involved in pulmonary dmg delivery of glucocorticoids have been reviewed. Among these, low oral bioavailability, high pulmonary deposition, pronounced clearance, and sustained pulmonary release are the most important parameters to be considered. 

L. L. Boles Ponto and J. A. Ponto, Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part I), Clin. Pharmacokinet. 22 211-222 (1992). 

Combined pharmacokinetic-dynamic studies seek to characterize the time course of drug effects through the application of mathematical modeling to dose-effecttime data. This definition places particular emphasis on the time course of drug... 

As is implicit from all the above, the measured concentration in plasma is directly linked to the observed effect for these simple mechanistic, pharmacokinetic-dynamic models. Accordingly, these models are called direct-link models since the concentrations in plasma can be used directly in (10.6) and (10.7) for the description of the observed effects. Under the assumptions of the direct-fink model, plasma concentration and effect maxima will occur at the same time, that is, no temporal dissociation between the time courses of concentration and effect is observed. An example of this can be seen in the direct-fink sigmoid Emax model of Racine-Poon et al. [418], which relates the serum concentration of the anti-immunglobulin E antibody CGP 51901, used in patients for the treatment of seasonal allergic rhinitis, with the reduction of free anti-immunglobulin E. 

When a lag time of E (t) is observed with respect to the c (t) time course, the use of a combined pharmacokinetic-dynamic model, the indirect-link model, is needed to relate the drug concentration c (t) to the receptor site drug concentration y (t) (which cannot be measured directly) and the y (t) to the pharmacological response E (t).1... 

Numerous applications of pharmacokinetic-dynamic models incorporating a biophase (or effect) compartment for a variety of drugs that belong to miscellaneous pharmacological classes, e.g., anesthetic agents [419], opioid analgesics [420-422], barbiturates [423,424], benzodiazepines [425], antiarrhyth-mics [426], have been published. The reader can refer to a handbook [427] or recent reviews [405] for a complete list of the applications of the biophase distribution model. 

Ariens [432] was the first to describe drug action through indirect mechanisms. Later on, Nagashima et al. [433] introduced the indirect response concept to pharmacokinetic-dynamic modeling with their work on the kinetics of the anticoagulant effect of warfarin, which is controlled by the change in the prothrombin complex synthesis rate. Today, indirect-response modeling finds extensive... 

All the above-mentioned pharmacokinetic-dynamic models are characterized by reversibility of the drug-receptor interaction. In several cases, however, drug action relies on an irreversible bimolecular interaction thus, enzyme inhibitors and chemotherapeutic agents exert their action through irreversible bimolecular interactions with enzymes and cells (bacteria, parasites, viruses), respectively. 

Using the approach of Sheiner and Verotta [452], a large number of pharmacodynamic models can be considered as hierarchical models composed of a series of submodels. These submodels are linear or nonlinear, static or dynamic input-output, elementary models. Several possible combinations of such submodels have been considered, but they have systematically associated the linear with dynamic features, and the nonlinear with static ones. Is there hesitation or fear of using nonlinear dynamics in the traditional pharmacokinetic-dynamic modeling context ... 

The fundamental assumption and equations governing the effect-concentration relationship for each one of the models considered are listed in Table 10.1. The presence or not of an hysteresis loop in the effect-plasma concentration plot of each model is also quoted in Table 10.1. At present, the methodology for performing efficient pharmacokinetic-dynamic modeling is well established [405,456,457],... 

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