Drug distribution overview

Satake H, Kawada T (2006) Overview of the primary structure, tissue distribution, and function of tachykinins and their receptors. Curr Drug Targets 7 963-974... 

This chapter will review some of the important methods for carrying out in vivo absorption and bioavailability studies, as well as attempt to provide an overview of how the information may be used in the drug discovery process. The chapter is aimed at medicinal chemists and thus will focus on the use of animals in discovery phase absorption, distribution, metabolism, and excretion/pharmacokinetic (ADME/PK) studies, rather than the design of studies that are for regulatory submission, or part of a development safety package. 

Membrane permeability is one of the most important determinants of pharmacokinetics, not only for oral absorption, but also for renal re-absorption, biliary excretion, skin permeation, distribution to a specific organ and so on. In addition, modification of membrane permeability by formulation is rarely successful. Therefore, membrane permeability should be optimized during the structure optimization process in drug discovery. In this chapter, we give an overview of the physiology and chemistry of the membranes, in vitro permeability models and in silica predictions. This chapter focuses on progress in recent years in intestinal and blood-brain barrier (BBB) membrane permeation. There are a number of useful reviews summarizing earlier work [1-5]. 

Perspectives of the requirements for the development of leads and drugs have been summarized in an overview paper °° The chemical features should be amenable to optimization, the patient situation should be favorable, absorption and other distribution properties should be good. A set of measurable items can help to appraise such determinants. 

Fig. 1. Overview of pharmacology. Pharmacokinetics (PK) relates to the effect of the body on the drug and principally includes bioavailability, distribution, and clearance. Pharmacodynamics (PD) relates to drug concentration and receptor availability. The response to drug concentrations may be therapeutic, subtherapeutic, or toxic, depending on considerations involving both PK and PD principles. From Linder MW, Valdes R Jr. Pharmacogenetics fundamentals and applications. Therapeutic drug monitoring and toxicology. AACC 1999 20(l) 10 with permission.)...

In the first part of this overview (Sections II, III, IV and V) some physiological aspects of drug absorption, distribution and elimination will be discussed. The second part (Sections VI and VII) will briefly focus on some pharmacokinetic parameters and terminology and on variability in pharmacokinetics. Due to its limited size, this chapter only includes some basic and general information. For more... 

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