Pharmacokinetic models basic

Pharmacokinetics is defined as the study of the quantitative relationship between administered doses of a drug and the observed plasma/blood or tissue concentrations.1 The pharmacokinetic model is a mathematical description of this relationship. Models provide estimates of certain parameters, such as elimination half-life, which provide information about basic drug properties. The models may be used to predict concentration vs. time profiles for different dosing patterns. 

Yokogawa K, IshizakiJ, Ohkuma S, Miyamoto K. Influence of lipophilicity and lysosomal accumulation on tissue distribution kinetics of basic drags a physiologically based pharmacokinetic model. Methods Find Exp Clin Pharmacol. 2002 24 81-93. 

Germani, M., Crivori, P., Rocchetti, M., Burton, P.S., Wilson, A.G.E., Smith, M.E. and Poggesi, I. (2007) Evaluation of a basic physiologically-based pharmacokinetic model for simulating... 

The studies reported here are oriented toward enunciating the basic mechanisms of the disease rather than improving the existing model by curve fitting. Because the population response to the disease exhibits wide variance, the dose-response characteristics of the animal must be incorporated into the model. This blending of pharmacokinetic models and dose-response models provides more insight into the etiology of the disease than has been available. 

These data clearly demonstrate that IPPSF flux profiles can be charactoized by five physical chemical parameters (H-acidity, H-basicity, S-Polarizability, and HjO solubility). The correlation of the AUC of the IPPSF flux profile to these parameters was high = 0.978), an important finding because AUC from skin would be the prime measure of systemic exposure in a toxicological risk assessment and could serve as the input function for a physiologically based pharmacokinetic model for a compound. The IPPSF efflux profile from skin reflected by its AUC has been previously used as the input profile for predicting in vivo human plasma-concentration time profiles after transdermal drug delivery (Riviere, Williams, etal., 1992). 

Whereas classical pharmacokinetic models utilize a relatively small number of compartments (see Figure. 6.10), PBPK models seek to mimic physiological pathways and processes controlling the time-course of plasma and tissue concentrations and represent the state-of-the-art in advanced pharmacokinetic systems analysis. Basic concepts of PBPK modeling and a hybrid application to composite nanodevice pharmacokinetics are described in this section. 

The acidity or basicity of compounds, as expressed by the pAl, is another property of bioactive compounds. This can have substantial influence on aqueous solubility and pharmacokinetics. Models for pK, employing neural nets are still emerging although prior experiences with other properties and the recent work by Clark (111) suggest that neural networks have a useful role in modeling this important property. 

In this section we review some of the simplest pharmacokinetic models which contain mass transfer coefficients. We do so only to illustrate the basic ideas involved more complete analyses for specific drugs are beyond the scope for this book. To begin, we consider how we can easily measure blood flow in one artery. One way is to inject a known mass M of a nonadsorbing solute into the artery and measure the downstream concentration ci spectrophotometrically as a function of time. From a mass balance... 

Sharma, A. and Jusko, W.J., Characterization of four basic models of indirect pharmacodynamic responses, /. Pharmacokinet. Biopharm., 24,611-635,1996. 

Parrott, N., Jones, H., Paquereau, N. and Lave, T. (2005) Application of fidl physiological models for pharmaceutical drug candidate selection and extrapolation of pharmacokinetics to man. Basic Clinical Pharmacology and Toxicology, 96, 193—199. 

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