• High distribution rate - drug reaches to the site of action quickly - fast drug effect (i.e.

short
onset time).

• High distribution extent - drug reaches to a large portion of the body - long residence time
in the body - prolonged therapeutic duration.

• High Blood flow rate -- Increased rate of drug transfer --Decreased equilibration time

• High permeability rate -- Increased rate of drug transfer -- Decreased equilibration time

• Plasma protein binding is a reversible process.

• Drugs that are highly bound to plasma protein have low distribution extent and distribution
volume

• Drugs that are highly bound to plasma protein have slow elimination rate, long half-life and
residence time in the body

• Drugs having high affinity to the tissues are characterized by large distribution extent and
distribution volume

• Distribution volume normalized by body weight of polar and water soluble drugs (e.g.
digoxin, antipyrene, gentamicin) increases in newborns and decreases in obesity.

• Distribution volume normalized by body weight of non-polar and lipid soluble drugs (e.g.
barbiturates) decreases in newborns and increases in obesity.

• Vd is not constant; it increases with time and plateaus when equilibrium is reached.

• Vd (normalized by body weight) measures distribution extent − Large normalized Vd

indicates large distribution extent.

• elimination extent is always 100%

• Increasing elimination rate decreases drug plasma concentration and thus reduces drug
pharmacological effect.

• Decreasing elimination rate increases drug plasma concentration and thus produces dose-
dependent toxicity. And prolongs the life of the drug in the body and thus extends drug
therapeutic duration.

• k (Elimination rate constant) is directly proportional to elimination rate.

• t0.5 is inversely proportional to elimination rate.

• Large CL (𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒) indicates fast elimination

Applications 𝐶𝑙𝑒𝑎𝑟𝑎𝑛𝑐𝑒:
• CL is used for calculation of the maintenance dose.
• CL is used for calculation of the average steady state concentration

Applications of Apparent volume of distribution:

• Vd is used to identify the distribution pattern that characterizes a particular drugs.
• calculation of the loading dose.

• Rate of drug metabolism is described by Michaelis- Menten equation

• Increasing hepatic clearance decreases drug plasma concentration and thus reduces drug
pharmacological effect.

• Increasing blood flow to the liver increases hepatic clearance.

• In neonates, elderly, hepatic, kidney, and cardiac diseases, hepatic clearance is slower than
in healthy adults.

• highly bound to plasma protein have slow hepatic clearance

• Increasing metabolic activity of the enzymes increases rate of metabolism of their

substrates, thus increases hepatic clearance.

• Drug metabolism is slower in neonates (due to immaturity of enzymes) and elderly humans
(due to lower enzymatic activity).

• Females metabolize alcohol more slowly than males

• Rapid metabolizers are prone to reduced drug effect.

• Slow metabolizers are prone to dose-dependent toxicity.

• People who acetylate warfarin slowly (slow acetylators) are subject to excessive bleeding.
• People who acetylate phenytoin slowly (slow acetylators) are subject to ataxia.

• Biliary secretion promotes hepatic clearance, while intestinal reabsorption reverses it.

• t0.5 and t0.9 are inversely proportional to reaction rate constants.