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Unformatted text preview: OVERVIEW We emphasised in Chapters 2 and 3 that drugs, being molecules, produce their effects by interacting with other molecules. This interaction can lead to effects at all levels of biological organisation, from molecules to human populations (Fig. 6.1). 1 In this chapter, we cover the principles of metrication at the various organisational levels, ranging from laboratory methods to clinical trials. Assessment of drug action at the population level is the concern of pharmacoepidemiology and pharmacoeconomics (see Ch. 1), disciplines that are beyond the scope of this book. We consider first the general principles of bioassay, and its extension to studies in human beings; we describe the development of animal models to bridge the predictive gap between animal physiology and human disease; we next discuss aspects of clinical trials used to evaluate therapeutic efficacy in a clinical setting; finally, we consider the principles of balancing benefit and risk. Experimental design and statistical analysis are central to the interpretation of all types of pharmacological data. Kirkwood & Sterne (2003) provide an excellent introduction. 87 6 Method and measurement in pharmacology BIOASSAY Methods for measuring drug effects are needed in order that we may compare the properties of different substances, or the same substance under different circumstances, requirements that are met by the techniques of bioassay , defined as the estimation of the concentration or potency of a substance by measurement of the biological response that it produces. USES OF BIOASSAY The uses of bioassay are: • to measure the pharmacological activity of new or chemically undefined substances • to investigate the function of endogenous mediators • to measure drug toxicity and unwanted effects. ▼ Bioassay plays a key role in the development of new drugs, discussed in Chapter 56. In the past, bioassay was often used to measure the concentration of drugs and other active substances in the blood or other body fluids, an application now superseded by analytical chemistry techniques. Bioassay is useful in the study of new hormonal or other chemically mediated control systems. Mediators in such systems are often first recognised by the biological effects that they produce. The first clue may be the finding that a tissue extract or some other biological sample produces an effect on an assay system. For example, the ability of extracts of the posterior lobe of the pituitary to produce a rise in blood pressure and a contraction of the uterus was observed at the beginning of the 20th century. These actions were developed as quantitative assay procedures, and a standard preparation of the extract was established by international agreement in 1935. By use of these assays, it was shown that two distinct peptides— vasopressin and oxytocin —were responsible, and they were eventually identified and synthesised in 1953. Biological assay had already revealed much about the synthesis, storage and release of the...
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This note was uploaded on 10/28/2011 for the course BIOR 14 taught by Professor Bs during the Winter '11 term at Lund.
- Winter '11