BIOPHARMACEUTICS AND

PHARMACOKINETICS
DISTRIBUTION PROCESS
Distribution
 The process by which a drug reversibly
leaves the blood stream and enters the
interstitium and then cells
 For an IV drug; No absorption occurs
 Distribution occurs immediately after
administration
Physiologic Factors affecting
distribution:
1. Cardiac output
 volume of blood pumped by the heart per
minute
 Px with CHF may have delayed drug effect
due to poor distribution
2. Regional blood flow
 % of CO that reaches specific tissue
 Organs w/ high RBF:
◦ liver (25%), kidney(25%), lungs(100%), brain)
 Organs with low RBF
◦ bone, adipose)
 Capillary Permeability- delivery
oxygenated blood to tissues; smallest vein
3. Capillary Permeability
Depends on
 Capillary structure
 Chemical nature of the
drug

4. Liphophilicity of the
drug
Two important parameters of drug
distribution:
1. Protein binding (PB)
2. volume of distribution (Vd)
Protein binding
 limits the access of drugs to certain body
compartment.
 binding of the serum proteinsdecreases
distribution
 Free form (unbound) can reach the site of
action, metabolized, excreted
 Bound form (serves as reservoir)
Examples of proteins & substrates
 Albumin weak acidic (dominant)
 Alpha 1 glycoprotein weak basic drugs
 Globulin binding hormones
Significant of PB
 Provide slow release form of a drug
(repository, resulting to extended affect).
 Limits access to certain body compartment
 Can make the drug prone to drug-drug
interaction

Examples of drugs with high protein binding:

 Diazepam, Indomethacin, Tolbutamide,
Warfarin, Midazolam
Volume of distribution (Vd)
 Mathematical relationship between the
total amount of drug in body and the
concentration of drug in the blood
 It is the hypothetical volume of fluid
where drug is disposed.
 useful for calculating the loading dose of a
drug
Example:
 If 10 mg of a drug are injected and the
plasma concentration is 1 mg/L what is
Vd?
 Vd= Dose = 10 = 10 L
C0 1
Examples of drugs with high Vd:
 Atropine
 Chloroquine
 Digoxin
 Fluoxetine
 Imipramine & TCAs
 Beta blockers
Examples of Drugs with low Vd:
 Chlorpropamide
 Furosemide
 Tolbutamine
 Valproic Acid
 Warfarin
Significance: Management of
Toxicities/ drug overdose
 Drugs w/ low Vd= hemodialysis
(alternative treatment)
 Drugs w/ high Vd = hemodialysis (useless)
Plasma half-life of drugs
 Length of time needed to decrease drug
plasma concentration by one half
 The greater the half-life of the drug, the
longer it takes to excrete
 Determines frequency and dosages
Example:
 If paracetamol 500mg/tab has half-life of 4
hours, how long will it take until the
blood concentration of this drug falls to
25% of its initial strength?
**END of DISCUSSION**