Anatomical-physiological approaches in pharmacokinetics and pharmacodynamics.
Use of an anatomical-physiological approach allows an investigator an alternative to regarding the whole body as a 'black box' producing biofluid specimens for drug assay, and then blindly applying a formula-driven mathematical approach to determine the pharmacokinetics and pharmacodynamics of the drug of interest. Instead, it means the investigator can consider that the body is the sum of interacting parts or regions connected anatomically by blood flow carrying the drug of interest, that the regions as well as the carrier blood are not homogeneous because each has a physiological role, and that the parts or regions are connected neurally and humorally so that the response in any region or part of the system may be modified by and/or modulate effects at another region or part. Such an approach is difficult to institute experimentally because a complicated (and often expensive) preparation is usually required in animal studies, and is rarely possible in research with humans because of ethical constraints. Despite these restrictions, there are many examples of the use of an anatomical-physiological approach allowing greater insight into pharmacological problems than would have been possible with a conventional 'whole body' approach alone. This paper takes a number of examples from the discipline of anaesthesia and pain management and groups them to illustrate the principles of the approach regarding drug arterio-venous equality and tissue distribution, multiple sites of clearance and multiple sites of action.
Mather
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Centre for Anaesthesia and Pain Management Research, University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
D000701:Analgesics, Opioid / Q000493:pharmacokinetics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D010599:Pharmacokinetics; D010600:Pharmacology; D013237:Stereoisomerism; D014018:Tissue Distribution
D000701:Analgesics, Opioid; D000779:Anesthetics, Local