General Principles Of Pharmacology/Three basic concepts
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Three Basic Concepts
Half-life
The half-life (t1/2) is the time taken for the drug concentration to decline by 50%. It is related to the rate constant by the following:
t1/2 = ln (2)/k = 0.693/k
In the simplest cases, the half-life does not change with dose (this is always true for first-order elimination).
Half-life is rarely an absolute constant, it is affected by physiologic, pathologic, and environmental factors, so that individual patients have their own half-life values for each drug.
Note that: 90 % of the drug is lost in 3.32 half-lives
95 % of the drug is lost in 4.32 half-lives
99 % of the drug is lost in 6.64 half-lives
Apparent volume of distribution
The apparent volume of distribution (Vd) is the volume of fluid which the drug would occupy if it were evenly distributed through that volume at the concentration measured in the plasma (central compartment). In veterinary medicine it is usually expressed in liters/kg since animals vary enormously in size.
The volume of distribution is purely hypothetical and does not represent an actual physical volume inside the animal. Indeed,
when a drug binds preferentially to tissues at the expense of plasma (e.g., a drug that is highly lipophilic and partitions into
fat), the plasma concentration will be extremely low. This will result in a huge apparent volume of distribution, which may be
larger than the actual volume of the animal itself (>1L/kg). It is possible for Vd to be close to a recognizable volume, such
as plasma volume (~0.05 L/kg), extra cellular fluid (~0.2 L/kg), or total body water (~0.7 L/kg). This would happen if the drug
is uniformly distributed in one of these "compartments", but this is rare.
The Vd is basically a convenient method for describing how well a drug is removed from the plasma and distributed to the tissues.
However, it doesn't provide any specific information about where the drug is or whether it is concentrated in a particular organ.
A large volume of distribution implies wide distribution, or extensive tissue binding, or both. Conversely, ionized drugs that
are trapped in plasma, will have small volumes of distribution.
Compartmentalization
A compartment represents all those organs, tissues, and cells for which the rates of uptake and subsequent clearance of a chemical are sufficiently similar to prelude kinetic resolution. In other words, if you cannot distinguish the kinetics in more than one organ, tissue or cell, the group is taken as a compartment. This is a hypothetical concept which in some cases my not bear any resemblance to a physiological correlate.
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