Pharmacokinetics system

Pharmacokinetics Systemically absorbed to some degree. Protein binding 60%. Distributed extensively in red blood cells. Sites of metabolism have not been established. Metabolized to active and inactive metabolites. Primarily excreted unchanged in urine. 

Pharmacokinetics Systemic absorption is rapid following aerosol administration however, serum concentrations at recommended doses are very low. Metabolized in liver. Excreted in urine primarily as glucoside metabolite. Half-life Unknown. 

Pharmacokinetics Systemic absorption of tetracaine is variable. Metabolized by plasma pseudocholinesterase. Excreted in the urine. 

Pharmacokinetics Systemically absorbed, approximately 4%-17%. Protein binding Low. Not metabolized. Partially excreted unchanged in urine. Half-life 1.6-5.1 hr. 

P. Veng-Pedersen, Novel deconvolution method for linear pharmacokinetic systems with polyexponential impulse response, J. Pharm. Sci.,... 

A general understanding of the definitions of linear and nonlinear will be helpful when discussing drug input into the body, whether that dose or input is delivered by classic delivery means or by novel controlled release delivery systems. Linear and nonlinear pharmacokinetics are differentiated by the relationship between the dose and the resulting drug concentration. A linear pharmacokinetics system exhibits a proportional relationship between dose and Cp for all doses, whereas nonlinear pharmacokinetics systems do not. 

H. Cheng, W. R. Gillespie, and W. J. Jusko. Review article mean residence time concepts for non-linear pharmacokinetic systems. Biopharm. Drug Dispos. 15 627-641, 1994. 

D Argenio, 0. Z. Schumitzky, A. "A Program for Simulation and Parameter Estimation in Pharmacokinetic Systems," Comput. Programs in Biomed., 1979, 9, 115-134. 

Pharmacokinetic studies are in general less variable than pharmacodynamic studies. This is so since simpler dynamics are associated with pharmacokinetic processes. According to van Rossum and de Bie [234], the phase space of a pharmacokinetic system is dominated by a point attractor since the drug leaves the body, i.e., the plasma drug concentration tends to zero. Even when the system is as simple as that, tools from dynamic systems theory are still useful. When a system has only one variable a plot referred to as a phase plane can be used to study its behavior. The phase plane is constructed by plotting the variable against its derivative. The most classical, quoted even in textbooks, phase plane is the c (f) vs. c (t) plot of the ubiquitous Michaelis-Menten kinetics. In the pharmaceutical literature the phase plane plot has been used by Dokoumetzidis and Macheras [235] for the discernment of absorption kinetics, Figure 6.21. The same type of plot has been used for the estimation of the elimination rate constant [236]. 

Conceiving models based on block diagrams may be quite complex, involving feedback loops and time delays. A paper [361] shows in detail how such a model can be constructed for a pharmacokinetic system. On the other hand, retentiontime reversible models can be very powerful and flexible for simulation and data fitting. 

Tsokos, J. and Tsokos, C., Statistical modeling of pharmacokinetic systems, Journal of Dynamic Systems, Measurement, and Control, Vol. 98, 1976, pp. 37-43. 

Durisova, M., Dedik, L., and Balan, M., Building a structured model of a complex pharmacokinetic system with time delays, Bulletin of Mathematical Biology, Vol. 57, No. 6, 1995, pp. 787-808. 

Cheng, H. Gillespie, W.R. Jusko, W.J. Mean residence time concepts for non-linear pharmacokinetic systems. Biopharm Drug Dispos. 1994, 15 (8), 627-641. 

Veng PP. Novel Deconvolution Method for Linear Pharmacokinetic Systems with Polyexponential Impulse Response.]Pharm Sci 1980 69 312-318. 

M. Verstraete, H. Bounameaux, F. de Cock, F. van de Werf, and D. J. Collen. Pharmacokinetic systemic fibrinolytic effects of recombinant human tissue-type plasminogen activator (rt-PA) in humans. Pharmacol. Exper. Ther. 255 506 (1985). 

For a linear pharmacokinetic system, measures of exposure, such as maximal concentration (Cmax) or area under the curve from 0 to infinity (AUC), are proportional to dose... 

Schumitzky, A. (1986). Stochastic control of pharmacokinetic systems. In Topics in Qinicai Pharmacology and Therapeutics" (R. F. Maronde, ed.), pp. 13-25, Springer-Verlag, New York. 

Berezhkovskiy LM. 2004. Volume of distribution at steady state for a linear pharmacokinetic system with peripheral elimination. 

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. 

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