Pharmacokinetics -- part 1 -- W.M. Tom
Department of Pharmacology
University of Hong Kong
Pharmacokinetics -- part 1 -- W.M. Tom
Department of Pharmacology
University of Hong Kong
Pharmacokinetics -- refers to the action of the body on the drug, including:
absorption
distribution
elimination -- metabolism & excretion
Drug Disposition
Drug Absorption Peroral administration (P.O. route)
swallowing
commonly known as “oral administration”
most convenient and economic method of systemic drug delivery
dosage forms, e.g. tablets, capsules, syrups, etc.
Drug absorption
Solids are not absorbed! Dissolution is usually the rate limiting step!
Drug absorption stomach (pH 1~3) in favour of weak acid absorption duodenum (pH 5~7) in favour of weak base absorption ileum (pH 7~8) in favour of weak base absorption
Diffusion Across Membrane
Weak
Acid Weak
Base B BH+ (pH > pKa ) (pH > pKa ) (pH < pKa ) (pH < pKa ) HA A-
Drug Absorption Factors affecting drug absorption by enteral routes
1. Drug dissolution
-- depends on drug formulation of oral preparations
2. pH environment in GI tract
-- unionized form efficiently absorbed
3. Lipid solubility of the drug
-- nonpolar form easily absorbed
Drug Absorption Factors affecting drug absorption by enteral routes
4. Effects of food
-- in general delays drug absorption
5. First pass effect
-- absorption of a drug into the portal circulation
-- drug metabolized by liver before it reaches the systemic circulation
First-pass effect mouth esophagus stomach small intestine colon rectum
First - Pass Effect
Drug Absorption Parenteral routes
1. intravenous injection (IV)
-- directly into a vein
-- 100% bioavailability
2. intramuscular injection (IM) -- into a muscle
-- depends on blood supply
Drug Absorption Parenteral routes
3. subcutaneous injection (SC)
-- under the skin
-- intended for slow absorption
4. others -- inhalation
-- sublingual
-- topical
-- transdermal, etc.
Absorption, distribution, metabolism and excretion
Drug Distribution Drug transfer to various tissues
-- depends on drug lipophilicity and blood flow
Drug barriers
-- e.g. blood-brain barrier, placenta
Drug binding to plasma proteins
-- bound drugs are pharmacologically inactive
-- unbound drugs are free to distribute to target tissues
-- different drugs may compete for binding to plasma proteins and displace each other from binding sites
Bound Free Free Bound LOCUS OF ACTION
“RECEPTORS” TISSUE
RESERVOIRS SYSTEMIC
CIRCULATION Free Drug Bound Drug ABSORPTION EXCRETION BIOTRANSFORMATION
Comments