Pharmacokinetics drug absorption

The issues related to pharmacokinetics - drug absorption, distribution, metabolism, excretion - have always been important to the success of the drug discovery process. In many cases, not enough attention was paid to these factors in the early stages of the discovery... 

This generally describes the process of drug absorption into the body, distribution throughout the body, metabolism by degrad a tive and metabolizing enzymes in the body, and finally elimination from the body. It is useful to consider each of these steps because together they summarize pharmacokinetics. 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

Van de Waterbeemd, H., Smith, D. A., Beaumont, K., Walker, D. K. Property-based design optimization of drug absorption and pharmacokinetics. 

Stirred tank models have been widely used in pharmaceutical research. They form the basis of the compartmental models of traditional and physiological pharmacokinetics and have also been used to describe drug bioconversion in the liver [1,2], drug absorption from the gastrointestinal tract [3], and the production of recombinant proteins in continuous flow fermenters [4], In this book, a more detailed development of stirred tank models can be found in Chapter 3, in which pharmacokinetic models are discussed by Dr. James Gallo. The conceptual and mathematical simplicity of stirred tank models ensures their continued use in pharmacokinetics and in other systems of pharmaceutical interest in which spatially uniform concentrations exist or can be assumed. 

The CAT model estimates not only the extent of drug absorption, but also the rate of drug absorption that makes it possible to couple the CAT model to pharmacokinetic models to estimate plasma concentration profiles. The CAT model has been used to estimate the rate of absorption for saturable and region-depen-dent drugs, such as cefatrizine [67], In this case, the model simultaneously considers passive diffusion, saturable absorption, GI degradation, and transit. The mass balance equation, Eq. (51), needs to be rewritten to include all these processes ... 

DM Oh, PJ Sinko, GL Amidon. Predicting oral drug absorption in humans A macroscopic mass balance approach for passive and carrier-mediated compounds. In DZ D Argenio, ed. Advanced Methods of Pharmacokinetic and Pharmacodynamic Systems Analysis. New York Plenum Press, 1990, pp 3-11. 

GD Leesman, PJ Sinko, GL Amidon. Simulation of oral drug absorption Gastric emptying and gastrointestinal motility. In PG Welling, FLS Tse, eds. Pharmacokinetics. 2nd ed. New York Marcel Dekker, 1989, pp 267-284. 

K. Luthman, and P. Artursson. Theoretical predictions of drug absorption in drug discovery and development, Clin. Pharmacokinet. 2002, 41, 877-899... 

Zhang, Y., Benet, L. Z., The gut as a barrier to drug absorption combined role of cytochrome P450 3A and P-glycoprotein, Clin. Pharmacokinet. 

L. H., Karim, A., Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications, Clin. Pharmacokinet. 1999, 36, 233—254. 

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