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Drug distribution tissue barriers

Consequently, bioavailability depends on the route of administration as well as the drug s ability to cross membrane barriers. Once in the systemic circulation, further distribution into peripheral tissues may also be important in allowing the drug to reach the target site. Many drugs must eventually leave the systemic capillaries and enter other cells. Thus, drugs have to move across cell membranes and tissue barriers to get into the body and be distributed within the body. In this section, the ability of these membranes to affect absorption and distribution of drugs is discussed. [Pg.17]

In some instances, P-gp can significantly affect the profile of drug distribution from systemic circulation into organs and tissues, most notably those that possess a specialized blood-tissue barrier such as the brain. Experiments with mdrla(—/—) mice have shown how P-gp affects the distribution of its substrates into certain tissues (11,12,124,212-219). A few examples are shown below to demonstrate the role played by P-gp in the tissue distribution of drugs. [Pg.377]

In the foregoing sections, pharmacon metabolism has been considered in relation to the pharmacodynamic, especially toxic aspects of action. Drug distribution also plays a role in the pharmacodynamic phase of drug action. Modulation of drug distribution, for instance, exclusion of penetration of particular barriers in the organism (e.g. the blood-brain barrier), or preferential bioactivation or bioinactivation in particular tissues, can modulate the spectrum of action of compounds and possibly exclude particular undesired effects. [Pg.25]

Hyoscyamine is well distributed throughout the body. The drug crosses the blood-brain barrier. It also crosses the placenta and found in placental tissues. Small quantities of the drug distribute into breast milk. Hyoscyamine is about 50% bound to plasma proteins (51,52). [Pg.182]

Technologies for isolating and cultivating endothelial and epithelial cells from many of the tissue interfaces influencing drug distribution have rapidly evolved in the past 20 years. As a consequence, the pharmaceutical scientist now has an assortment of cell culture systems to characterize fundamental drug delivery processes at the biochemical and molecular levels in major epithelial and endothelial barriers. [Pg.104]

In order to appreciate the role of biological membranes and tissue barriers as determinants of drug distribution, it is important to begin with an understanding of cell membranes. [Pg.116]

Both the rate and extent of drug distribution across tissue barriers can have a profound impact on pharmacokinetic and pharmacodynamic properties. The extent of drug distribution manifests itself locally as the tissue to plasma (or blood) concentration ratio. Collectively, the extent of distribution into all the tissues results in the apparent volume of distribution. Simply put, the pharmacokinetic parameter volume of distribution reflects the ratio of individual tissue to plasma drug concentration weighed for tissue volume. The rate of distribution (together with the extent of distribution) can influence the shape of the plasma versus time profile for a drug, which can give rise to differences in elimination half-life as well as onset and duration of action. [Pg.126]

Although the general principles discussed here apply to all membranes, it is important to recognize that physiological (e.g., specific cell types, blood flow, and permeability) and molecular (e.g., uptake or efflux transporters) distinctions among tissue barriers can differentially affect drug distribution, which may be associated with efficacy or toxicity (Figure 7.10). [Pg.127]

Figure 7.10 Select tissues for which a blood-tissue barrier is thought to be of importance in limiting drug distribution. Figure 7.10 Select tissues for which a blood-tissue barrier is thought to be of importance in limiting drug distribution.
Figure 3.6 Illustration of the concepts of the apparent volume of drug distribution. Application of the beaker concept to the human body, which contains organs and tissues with lipophilic barriers. Figure 3.6 Illustration of the concepts of the apparent volume of drug distribution. Application of the beaker concept to the human body, which contains organs and tissues with lipophilic barriers.
Absorption is strictly related to gastric pH, drug solubility or gastrointestinal motility, while distribution is influenced by competition of plasma protein binding, displacement from tissue-binding sites, or alterations in local tissue barriers. [Pg.51]


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