Drug development basic principles

B22. Brodie, B. B., Basic principles in development of methods for drug assay. In Concepts in Biochemical Pharmacology (B. B. Brodie and J. R. Gillette, eds.). Handbook of Experimental Pharmacology, Vol. 28, Part 2, pp. 1-8. Springer-Verlag, Berlin and New York, 1971. 

The development of the first transdermal patches in the 1980s generated considerable interest in this route of drug administration. Soon afterwards, iontophoresis was rediscovered and its potential to contribute to the new field of transdermal drug delivery was examined. This work provided the basic principles for modern iontophoretic devices [13,18-21]. Furthermore, and importantly, they demonstrated the existence of a (primarily) electroosmotic, convective solvent flux during transdermal iontophoresis [10,11,22-24], and it was shown that the permselective properties of the skin (a) could be exploited to enhance the transport of neutral, polar species and (b) have a clear impact on ionic transport. Subsequent research has better characterized skin permselectivity and the factors which determine the magnitude of electroosmosis [25-27],... 

This chapter has reviewed the basic principles of computer-aided drug design, and several strategies of how it can be successfully integrated with combinatorial chemistry to develop highly effective site-focused libraries. Diversity plays a key role, as the more diverse set of compounds tested that fit the site-focused criteria, the more information is retrieved to improve the site-focused definition, which further directs the search in diversity space. In addition, if good hits are found, the information can be fed back to find compounds close in diverse space to the hit. This new paradigm for structure-based combinatorial chemistry should provide a powerful tool for rapid discovery of novel, potent lead compounds in the years to come. 

Immunoassays which employ drugs labelled with a substance which emits light when activated have been developed. The basic principles of these assays are similar to those of fluoroimmunoassays. The use of luminescent labels, however, has the advantage that light is not introduced into the system, so giving an increase in sensitivity. 

This book describes how the basic principles of clinical pharmacology currently are being applied in the process of drug development. 

When Professor Ariens shook up the scientific community in 1984 by using such terms as "isomeric ballast" and "sophisticated nonsense in pharmacokinetics and clinical pharmacology" to describe the neglect of stereochemical factors for chiral compounds (3), this stimulated an explosive revival in the state of the science. The long-known basic scientific principles began to be applied to drug development, and today the pharmaceutical industry is very cognizant of the relevant issues (4-6), some of which are listed in Table 1. 

F. BressoUe, M. Audran, T.-N. Pham, and J-J. Vallon, Cyclodextrins and enantiomeric separations of drugs by liquid chromatography and capillary electrophoresis Basic principles and new developments, J. Chro-matogr. B 657 303 (1996). 

This chapter presents the basic principles of pharmacology upon which drug therapy is based. As you read the chapter, try to apply the principles to a drug with which you are familiar, like aspirin. Refer to this chapter often as you learn the drugs presented in the rest of the book. Try to learn the "story" of each drug rather than isolated facts. The best way to develop a story about a drug is to associate, ask, and predict... 

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