Principles, drug action

To make quantitative predictions of DDI for the new compound as perpetrator, a reliable estimate of a relevant in vivo concentration is needed. What is tmly needed is knowledge of the concentration of the inhibitor available to bind to the enzyme. For liver, if the well accepted free-dmg hypothesis (which underwrites fundamental drug action principles in pharmacology) is applied for DDI, then the use of a free intracellular liver concentration is needed. For inhibitors that are permeable through membranes, the free concentration in the portal vein should serve as the closest proxy for free intracellular concentration in the liver. Diminished permeability as well as active uptake and efflux from liver cells can confound this relationship. Nevertheless, use of estimates of unbound portal vein concentrations (which can be estimated from... 

Van Boxtel CJ, Holford NHG, Danhof M, editors. The in vivo study of drug action. Principles and applications of kinetic-dynamic modelling. Amsterdam Elsevier 1992. 

Tute, M. S. Lipophilicity a history. In Lipophilicity in Drug Action and Toxicology (Methods and Principles in Medicinal Chemistory), Pliska, V., Testa, B., Van de Waterbeemd, H. (eds.), Wiley-VCH, Weinheim, 1996, pp. 7-26. 

Limbird, L. E., Cell Surface Receptors A Short Course on Theory and Methods, 2nd ed., Nijhoff, Boston, 1996. Pratt, W. B. and Taylor, P., Principles of Drug Action, Churchill Livingstone, New York, 1990 (see, in particular, Chapters 1 and 2). 

Nebert DW, Weber WW. Pharmacogenetics. In Pratt WB, Taylor P eds. Principles of Drug Action The Basis of Pharmacology. New York Churchill Livingston, 1990. 

Examination of apparent exceptions to the free drug principle is important because such studies can lead to the identification of new processes that may be important for understanding drug action in certain circumstances. 

PK/PD models are obtained by combining a PK model (Section 13.2.4) and a PD model (Section 13.2.5), allowing the quantification of the relationship between drug administration and drug action. The principles of PK/PD modelling will be dealt with briefly. For a more detailed treatise, some excellent reviews can be found in the literature [21]. 

Mutschler E, Derendorf H. Drug actions—basic principles and therapeutic aspects. Stuttgart Medpharm Scientific Pub. Boca Raton CRC Press 1995. 

Gll. Goldstein, A., Aronow, L., and Kalman, S. M. Principles of Drug Action. The Basis of Pharmacology. Harper (Hoeber), New York, 1968. 

Classifying antiarrhythmic drugs is based on different principles for example, the location of the drug action. They can be substances that act directly on the myocardium and the conduction system of the heart itself, or substances that have an effect on the efferent... 

The potential of psychoactive TDM to improve therapy has been limited to date because many clinicians lack basic PK training and pharmaceutical marketing departments actively discourage TDM of their drugs. In order to correct this situation, clinicians must appreciate the basic PK principles necessary to correctly order and interpret TDM results, as well as to understand or predict drug actions in their individual patients. 

An often-misunderstood principle is that concentration in the blood rises until the rate of absorption equals the rate at which drug is being removed from the body (the so-called peak). This peak does not occur when absorption is complete but rather when the rate of absorption equals the rate of elimination. The time to peak is therefore determined by both absorption and elimination rates in the individual patient. Patients with faster elimination will have earlier peaks than will patients with slower elimination, even when the rate of drug absorption is the same (Fig. 4.2). The extent of absorption is usually expressed as the fraction absorbed or bioavailability. This is an important determinant of drug action. While rate and extent of absorption are related, they are different. In general, the onset and magnitude of effects are related to the rate of absorption, while the average steady state concentrations are related to the extent of absorption. 

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