Tissues blood perfusion

In PBPK models tissue blood perfusion and tissue composition can be characterized independently of the drug thus such a model can be created once and reused for many different drugs. Furthermore, because physical laws (mass conservation, diffusion, or facilitated transport mechanisms) are incor-... 

The absorption rate of drugs administered as intramuscular or subcutaneous injections may be affected in elderly because of reduced tissue blood perfusion. This is also true for transdermal administration, e.g. patches and gels, of drugs (Turnheim 2003). 

The distribution of a chemical in tissue depends on the binding/par-titioning between circulatory blood and tissues, the transfer across biological membranes and the tissue-blood perfusion. After incorporation, contaminants are distributed from blood to high perfusion tissues (e.g. liver, kidney), then to low perfusion ones (skin, muscle) and finally to lipoidal tissues [2], establishing kinetically different compartments (internal organs > liver > head skin) and different times to equilibrium [18]. Surfactants (LAS, AS, AES, AEO and APEO) have been... 

Since oxygen input to tissue depends upon tissue blood perfusion as well as oxyhemoglobin concentration, the latter was multiplied by a viscosity factor to account for perfusion changes resulting from the very high hematocrits that occur with severe hypoxia. Hematocrit was calculated from total red cell volume and total blood volume. The viscosity factor (Vi) was calculated from the relationship shown in Equation 5. 

Arkin, H., Holmes, K. R and Chen, M. M., 1987, Computer Based System for Continuous On-line Measurements of Tissue Blood Perfusion, Journal of Biomedical Engineering, 9 38-45. 

Intramuscular and subcutaneous injections are by far the most common means of parenteral drug administration. Because of the high tissue blood flow and the ability of the injected solution to diffuse laterally, drug absorption generally is more rapid after intramuscular than after subcutaneous injection. Drug absorption from intramuscular and subcutaneous sites depends on the quantity and composition of the connective tissue, the capillary density, and the rate of vascular perfusion of the area. These factors can be influenced by the coinjection of agents that alter local blood flow (e.g., vasoconstrictors or vasodilators) or by substances that decrease tissue resistance to lateral diffusion (e.g., hyaluronidase). 

The rate at which an equilibrium concentration of a drug is reached in the extracellular fluid of a particular tissue will depend on the tissue s perfusion rate the greater the blood flow the more rapid the distribution of the drug from the plasma into the interstitial fluid. Thus, a drug will appear in the interstitial fluid of liver, kidney, and brain more rapidly than it will in muscle and skin (Table 3.2). The pharmacokinetic concept of volume of distribution (a derived parameter that relates the amount of drug in the body to the plasma concentration) is discussed more fully in Chapter 5. 

Allopurinol also inhibits reperfusion injury. This injury occurs when organs that either have been transplanted or have had their usual blood perfusion blocked are reperfused with blood or an appropriate buffer solution. The cause of this injury is local formation of free radicals, such as the superoxide anion, the hydroxyl free radical, or peroxynitrite. These substances are strong oxidants and are quite damaging to tissues. 

There are several physiochemical properties of the toxicant that can influence its distribution. These include lipid solubility, pKa, and molecular weight, all of which were described earlier in this chapter (Section 6.4) and will not be described here. For many toxicants, distribution from the blood to tissues is by simple diffusion down a concentration gradient, and the absorption principles described earlier also apply here. The concentration gradient will be influenced by the partition coefficient or rather the ratio of toxicant concentrations in blood and tissue. Tissue mass and blood flow will also have a significant effect on distribution. For example, a large muscle mass can result in increased distribution to muscle, while limited blood flow to fat or bone tissue can limit distribution. The ratio of blood flow to tissue mass is also a useful indicator of how well the tissue is perfused. The well perfused tissues include liver,... 

---