One shot
Pharmacokinetics
what the body does to the drug.
absorption (A), distribution (D), metabolism (M) and excretion (E)
Influence of ph
Acidic drugs, e.g. aspirin (pKa 3.5) are largely unionized at acid gastric pH and are absorbed from
stomach,
while bases, [Link] (pKa 10) are largely ionized and are absorbed only when they reach the
intestines.
The unionized form of acidic drugs which crosses the surface membrane of gastric mucosal
cell, reverts to the ionized form within the cell then only slowly passes to the
extracellular fluid. This is called ion trapping.
Basic drugs attain higher concentration intracellularly.
Acidic drugs are ionized more in alkaline urine—do not back diffuse in the kidney
tubules and are excreted faster. Accordingly, basic drugs are excreted faster if urine is acidified.
ABSORPTION
Movement of a drug from the site of administration into the blood stream is known as
absorption.
Factors Influencing Drug Absorption
1. Physicochemical properties of the drug:
Physical state: Liquid form of the drug is better absorbed than solid formulations.
Lipid-soluble and unionized form of the drug is better absorbed than water- soluble and ionized form.
Particle size: Drugs with smaller particle size are absorbed better than larger ones, e.g. microfine
aspirin, digoxin and griseofulvin . Some of the anthelmintics have larger particle size.
Disintegration time: It is the time taken for the formulation (tablet or capsule)
to break up into small particles and its variation may affect the bioavailability.
Dissolution time: It is the time taken for the particles to go into solution. Shorter the time, better is the
absorption.
Formulations: Pharmacologically inert substances like lactose, starch, calcium sulphate, gum, etc. are
added to formulations as binding agents. These are not totally inert and may affect the absorption of
drugs, e.g. calcium reduces the absorption of tetracyclines.
Concentration
Area of absorbing surface
Vascularity of the absorbing surface
Route of administration –
Oral
effective barrier - epithelial lining of the gastrointestinal tract, which is lipoidal.
Presence of food dilutes the drug and retards absorption.
e.g. tetracyclines with calcium present in milk; moreover food delays gastric emptying.
Certain drugs are degraded in the gastrointestinal tract, e.g. penicillin G by acid, insulin by
peptidases, and are ineffective orally.
the oral absorption of certain drugs is low because a fraction of the absorbed drug
is extruded back into the intestinal lumen by the efflux transporter Pgp located in
the gut epithelium.
Inhibitors of Pgp - quinidine, verapamil, erythromycin
Pgp inducers like rifampin and phenobarbitone reduce the oral bioavailability
of these drugs.
Absorption of a drug can be affected by other concurrently ingested drugs. This may be a luminal effect:
formation of insoluble complexes,
e.g. tetracyclines and iron preparations with calcium salts and antacids, phenytoin with sucralfate. Such
interaction can be minimized by administering the drugs in 2 3 hour delay.
Alteration of gut flora by antibiotics may disrupt the enterohepatic cycling of oral contraceptives and
digoxin
BIOAVAILABILITY
It is a measure of the fraction (F ) of administered dose of a drug that reaches the systemic circulation in
the unchanged form. Intravenous route of drug administration gives 100% bioavailability.
drugs like lignocaine(liver) ventricular arrhythmias , isoprenaline (gut wall),
Enterohepatic cycling e.g. morphine and doxycycline.