Introduction to Veterinary Pharmacokinetics:  Home  Administration  Distribution  Elimination  Modeling  Models  Glossary 
Drug Distribution  

Volume of Distribution (V_{z}  also V_{d})  
The volume of fluid that "appears" to contain the amount of drug in the body (based on the plasma concentration).
Units

100 mg of a drug is added to a 10 liter fish tank filled with water. A sample is taken after equillibrium is reached. The chemical properties of the drug determine whether it stays in the water or sticks to the glass. more (new window) 
Representative (theoretical) volumes of distribution. Initial estimate of body water is 1 liter/kilogram (l/kg).  
Scenario  Physiologic Space  Volume of distribution 

Drug distributed only to plasma water  Blood volume = 7% of body weight Plasma water = 55% of blood volume 
1 l/kg x 0.07 x 0.55 = 0.0385 liters/kg 
Drug distributed evenly in extracellular fluid only  Extracellular fluid volume = 25% of body weight  1 l/kg x 0.25 = 0.25 liters/kg 
Drug distributed evenly extracellular + intracellular fluid only  Intracellular fluid volume = 40% of body weight  1 lg/kg x (0.25 + 0.40) = 0.65 liters/kg 
Drug distributed evenly in extracellular fluid and concentrated 3x in intracellular fluid  Extracellular fluid volume + 3x intracellular fluid volume  1 l/kg x (0.35 + (3 x 0.4)) = 1.45 liters/kg 
Drug Elimination  

Total Clearance (C_{lt})  
The volume of plasma water cleared of the drug during a specified time period.
Units:

A stylized representation of hepatic clearance. Note that extraction efficiency remains constant for both the initial condition and 30 minutes later. 10% of the drug molecules entering the liver are converted to metabolite. 
A direct answer to the question "How fast are drug concentrations falling?", λ_{z} is the slope of the natural log plot of the drug concentration versus time profile. It's related to clearance in that it's also the fraction of the volume of distribution cleared per unit time.
Units
Although the amount eliminated from the body is less and less for each time interval, the FRACTION of the amount eliminated during each interval is constant. This is demonstrated by the semilog plot. 
Semilogarithmic plot of hypothetical plasma concentration vs. time profile. Note that while this base10 log plot shows a straight line, the slope can only be calculated using natural logs. 
The time for elimination of one half of the total amount in the body. Units
Application(s) Tissue Residues
Approach to steady state

Approach to steady state. A stylized example in that the dose interval equals the drug halflife. 
Absorption  

Absorption rate constant (k_{a})  
The absorption rate constant describes the rate of drug movement (oral, IM, SC, etc.) from the dose to the circulatory system. In combination with other factors, ka determines the time required to reach the peak concentration (Cmax) following a dose of drug and the peak drug concentration. Units
Fraction of dose absorbed (F)When a drug is administered by any route OTHER than IV, it is rare that the entire dose is absorbed
Units
Application The fraction of the dose absorbed determines a drug's bioavailability (how much gets into the blood stream). Bioavailability is a common measure used to compare two different drug formulations (tablets vs. elixir) or to compare products sold by two different manufacturers (trade name drugs vs. generics). Bioavailability and BioequivalenceTwo drug products are bioequivalent if the nature and extent of therapeutic and toxic effects are equal following administration Although similar and related, equal bioavailability (F) does not guarantee bioequivalence. 
Two dose forms of the same drug are depicted. These two dose forms have equal fractions absorbed and equal rate constants of absorption. They are equally bioavailabile and they are bioequivalent. Two dose forms of the same drug are depicted. These two dose forms have equal fractions absorbed but very different rate constants of absorption. These two dose forms have equal bioavailability but they are not bioequivalent. 