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barriers in drug distribution
#1

Distribution (pharmacology)

Physical volume of an organism[edit]
This concept is related to multi-compartmentalization. Any drugs within an organism will act as a solute and the organism s tissues will act as solvents. The differing specificities of different tissues will give rise to different concentrations of the drug within each group. Therefore, the chemical characteristics of a drug will determine its distribution within an organism. For example, a liposoluble drug will tend to accumulate in body fat and water-soluble drugs will tend to accumulate in extracellular fluids. The volume of distribution (VD) of a drug is a property that quantifies the extent of its distribution. It can be defined as the theoretical volume that a drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. It can be determined from the following formula: {\displaystyle Vd={\frac {Ab}{Cp}}\,} {\displaystyle Vd={\frac {Ab}{Cp}}\,} Where: {\displaystyle Ab} Ab is total amount of the drug in the body and {\displaystyle Cp} {\displaystyle Cp} is the drug s plasma concentration.
As the value for {\displaystyle Ab} Ab is equivalent to the dose of the drug that has been administered the formula shows us that there is an inversely proportional relationship between {\displaystyle Vd} {\displaystyle Vd} and {\displaystyle Cp} {\displaystyle Cp}. That is, that the greater {\displaystyle Cp} {\displaystyle Cp} is the lower {\displaystyle Vd} {\displaystyle Vd} will be and vice versa. It therefore follows that the factors that increase {\displaystyle Cp} {\displaystyle Cp} will decrease {\displaystyle Vd} {\displaystyle Vd}. This gives an indication of the importance of knowledge relating to the drug s plasma concentration and the factors that modify it.
If this formula is applied to the concepts relating to bioavailability, we can calculate the amount of drug to administer in order to obtain a required concentration of the drug in the organism ('loading dose):
{\displaystyle Dc={\frac {Vd.Cp}{Da.B}} {\displaystyle Dc={\frac {Vd.Cp}{Da.B}}
This concept is of clinical interest as it is sometimes necessary to reach a certain concentration of a drug that is known to be optimal in order for it to have the required effects on the organism (as occurs if a patient is to be scanned).
Removal rate[edit]
A drug's removal rate will be determined by the proportion of the drug that is removed from circulation by each organ once the drug has been delivered to the organ by the circulating blood supply.[1] This new concept builds on earlier ideas and it depends on a number of distinct factors:
The drugs characteristics, including its pKa.
Redistribution through an organism s tissues: Some drugs are distributed rapidly in some tissues until they reach equilibrium with the plasma concentration. However, other tissues with a slower rate of distribution will continue to absorb the drug from the plasma over a longer period. This will mean that the drug concentration in the first tissue will be greater than the plasma concentration and the drug will move from the tissue back into the plasma. This phenomenon will continue until the drug has reached equilibrium over the whole organism. The most sensitive tissue will therefore experience two different drug concentrations: an initial higher concentration and a later lower concentration as a consequence of tissue redistribution.
Concentration differential between tissues.
Exchange surface.
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#2
Distribution in pharmacology is a branch of pharmacokinetics which describes the reversible transfer of drug from one location to another within the body.
Once a drug enters into systemic circulation by absorption or direct administration, it must be distributed into interstitial and intracellular fluids. Each organ or tissue can receive different doses of the drug and the drug can remain in the different organs or tissues for a varying amount of time.[1] The distribution of a drug between tissues is dependent on vascular permeability, regional blood flow, cardiac output and perfusion rate of the tissue and the ability of the drug to bind tissue and plasma proteins and its lipid solubility. pH partition plays a major role as well. The drug is easily distributed in highly perfused organs such as the liver, heart and kidney. It is distributed in small quantities through less perfused tissues like muscle, fat and peripheral organs. The drug can be moved from the plasma to the tissue until the equilibrium is established (for unbound drug present in plasma).
The concept of compartmentalization of an organism must be considered when discussing a drug s distribution. This concept is used in pharmacokinetic modelling.
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