Drug action distribution

Fig. 14. Schematic description of pharmacokinetic and pharmacodynamic determinants of drug action. Distribution from the measurement site (Cp) to the biophase (Ce), determined by a distribution rate constant is followed by drug-induced inhibition or stimulation of the production (k ) or removal (A out) of a mediator (R), transduction of the response R and further transformation of R to the measured effect E, if the measured effect variable is not R. (Modified from Jusko WJ, Ko HC, Ebling WF. Convergence of direct and indirect pharmacodynamic response models. J Pharmacokinet Biopharm 1995 23 5-6.)...

Neurotransmitter receptors have evolved as one of the key components in the ability of the central nervous system to coordinate the behaviour of the whole animal, to process and respond to sensory input, and to adapt to change in the environment. These same receptors are therefore ideal targets for drug action because of their central role in the activity of the nervous system. A rational approach to the development of new therapeutic strategies involving the action of drugs at receptors in the nervous system is based on knowledge of receptor structure, distribution and function. 

The Effect of Route of Administration and Distribution on Drug Action... 

The site of drug action and receptor distribution are being investigated 949 The mechanism of drug action may be elucidated by studying its binding 949... 

When levels of the drug decline in plasma, usually due to biotransformation and excretion, the drug then redistributes away from its site of action into other tissues (e.g., drugs may distribute across the placenta during pregnancy). This is a passive process, but lipid-soluble drugs penetrate the most. 

A Avdeef. Assessment of distribution-pH profiles. In Pliska, V., Testa B., van de Waterbeemd, H., eds. Lipophilicity in Drug Action and Toxicology. VCH Weinheim, Germany, 1996, pp 109-139. 

Goldstein, A., L. Aranow, and S. M. Kalman. 1974. Structure-activity (chapter 1) Drug absorption and distribution (chapter 2). In Principles of Drug Action The Basis of Pharmacology. New York Wiley. 

In mediating therapeutic response, protein pharmaceuticals are exposed to competing pathways of distribution in blood and highly perfused tissue that could sometimes produce untoward responses. Only a small fraction of drug is distributed to the sites of action. The schematic presented in Figure 13.2 depicts some of the... 

Changes in drug effects are often delayed in relation to changes in plasma concentration. This delay may reflect the time required for the drug to distribute from plasma to the site of action. This will be the case for almost all drugs. The delay due to... 

Goldstein A, Aronow L, Kalman SM (1968) The absorption, distribution and elimination of drugs — passage of drugs across the placenta. In Goldstein A, Aronow L, Kalman SM ed. Principles of drug action the basis of pharmacology. New York, Harper and Row, p 179. 

Pratt WB. The entry, distribution and elimination of drugs. In Pratt WB, Taylor P, eds. Principles of Drug Action. 3rd ed. New York Churchill Livingstone, 1990. 

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