PHARMACEUTICS AND PHARMACOKINETICS
absorption
When drug is taken by mouth, it undergoes 3
phases:
PHARMACEUTICS PHASE
▪ First phase of drug action
▪ drug becomes a solution so that it can cross
the biologic membrane
▪ 2 phases:
o Disintegration > Dissolution
PHARMACEUTICS PHASE
▪ Dissolution: a solid form must disintegrate
into small particles to dissolve into a liquid.
▪ EXCIPIENT: used in drug preparation to allow
the drug to take on a particular size and shape;
enhance drug dissolution
▪ Additives: ions potassium (K+) & sodium
(Na) e.g. :
PENICILLIN
PHARMACEUTICS PHASE
1. DISINTEGRATION: breakdown of tablet into
smaller particles
2. DISSOLUTION: dissolving of the smaller
particles in GI fluid before absorption
RATE LIMITING: is the time it takes the drug to
disintegrate and dissolve to become available
for body to absorb it.
❖Acidic fluid increase disintegration and
❖Food in GI may interfere with the
dissolution and absorption
FACTORS AFFECTING DISSOLUTION
▪ Form of drug ( LIQUID VS. SOLID) – liquids
more absorbed than solid, already in solution,
rapidly available for GI absorption
▪ Gastric pH (acidic vs. alkaline) – acidic media
faster disintegration & absorption
▪normal gastric pH: 1.5 – 3.5
▪ Age (young & elderly) increase pH decrease
absorption
FACTORS AFFECTING DISSOLUTION
Enteric coated drugs – resist disintegration in
gastric acid
▪ Disintegration occurs only in alkaline
environment ( intestine)
▪ Should not be crushed
Presence of food – interfere with dissolution &
absorption, enhance absorption of other drugs,
may be protectants of gastric mucosa.
Pharmacokinetics
▪ the study of the absorption, distribution,
biotransformation, and excretion of drugs.
▪ the process of drug movement to achieve drug
action.
▪ Specific processes are absorption,
distribution, metabolism and excretion
PHARMACOKINETIC PHASE
Four process are:
1. Absorption
2. Distribution
3. Metabolism (biotransformation)
4. Excretion (elimination)
Pharmacokinetics – Drug Transport Pathways
Three main pathways of drug movement across
cell membrane
 1. Most common is direct penetration by lipid
soluble drugs
2. 2nd pathway involves passage through
protein channels.
▪ Gates open and close either by voltage
gating or by assist of chemical substances (Na+
and K+ ions affecting some cardiac drugs)
3. 3rd is by carrier proteins that transport
molecules from one side of the cell membrane
to the other.
▪ An example would be oral drugs that carry
hormones to their sites of action
PHARMACOKINETIC PHASE
1. ABSORPTION
▪ the movement of drug particles from the GI
tract to body fluids by passive absorption, active
absorption, or pinocytosis.
▪ oral drugs are absorbed into the surface area
of the small intestine through the action of the
extensive mucosal villi.
(X) Protein-based drugs such as insulin and
growth hormones
Three Major Processes for Drug Absorption
1. Passive absorption – occurs mostly by
diffusion (movement from higher
concentration to lower concentration)
2. Active absorption – requires a carrier such as
an enzyme or protein to move the drug against
a concentration gradient.
3. Pinocytosis – is a process by which cells carry
a drug across their membrane by engulfing the
drug particles
ABSORPTION of Drugs
▪ drugs that are lipid soluble pass rapidly
through the GI membrane.
▪ Water-soluble drugs need a carrier, either
enzyme or protein, to pass through the
membrane.
▪ Certain drugs need acidic environment to
achieve greater drug absorption: antifungal &
calcium carbonate
▪ Hydrochloric acid destroys some drugs:
penicillin G
▪ Drugs administered by many routes do not
pass through the GI tract or liver
▪ Remember, drugs that are lipid soluble and
non-ionized are absorbed faster than water-
soluble and ionized drugs.
ABSORPTION
▪ Some drugs do not go directly into the
systemic circulation
▪ Pass from the intestinal lumen to the liver via
the portal vein.
▪ Hepatic first pass: process in which the drug
passes to the liver first
▪ Bioavailability is a subcategory of absorption.
▪ It is the percentage of the administered
drug dose that reaches the systemic circulation
and is available to act on body cells
BIOAVAILABILITY
Factors that alter bioavailability include:
1. drug form
2. route
3. GI mucosa and motility
4. Food and other drugs
5. changes in liver metabolism caused by liver
dysfunction
▪ IV administration is 100% bioavailable
▪ Subcutaneous and Oral route
▪ Mucous membranes allow for rapid and direct
absorption into the
bloodstream
DISTRIBUTION
▪ Involves the transport of drug molecules
within the body
▪ After the drug is absorbed into the
bloodstream, it is carried by the blood or tissue
fluids to its sites of pharmacologic action,
metabolism and excretion
▪ Protein binding is an important factor in drug
distribution
▪ Drug distribution into the CNS is limited
 ▪ Blood-brain barrier: composed of
capillaries with tight walls which limits
movement of drug molecules
▪ lipid soluble drugs and have a transport
system can cross the blood-brain barrier and
reach concentrations
▪ during pregnancy and lactation distribution of
drugs is unique - drugs cross the placenta and
pass into breast milk
PROTEIN BINDING
▪ Most drugs form a compound with plasma
proteins, mainly ALBUMIN, which act as carriers
▪ Only the free or unbound portion of a drug
acts on body cells
▪ As unbound drug acts on cells, the decrease in
plasma drug level causes some of the bound
drug to be released
▪ Protein binding allows a part of a drug dose to
be stored and released as needed
METABOLISM
▪ Method by which drugs are inactivated or bio
transformed by the body
▪ Some drugs yield metabolites that are also
active and exert effects on the body until they
are excreted (normeperidine)
▪ Most drugs are lipid soluble which aids their
passage across the cell membrane
▪ Excretion usually is by kidneys. Need to be
water soluble for this to occur.
▪ function of metabolism is to convert fat
soluble medications to water soluble ones.
▪ Hepatic drug metabolism or clearance is a
major mechanism for terminating drug action
and eliminating drug molecules from the body
▪ Most drugs are metabolized by the
cytochrome P450 enzymes in the liver
▪ Liver contains complex system of enzymes,
three of which are key in the metabolism of
medications/drugs
▪ Cytochrome p450
▪ enzymes catalyze the chemical reactions
which ultimately metabolize the medications
▪ Enzyme induction accelerates drug
metabolism.
HALF - LIFE
Half-life/ Elimination half-life (t 1⁄2) - time it
takes for one half of drug concentration to be
eliminated
▪ Short t 1/2 - 4 - 8hrs: given several times a day
(ex. Penicillin G)
▪ Long t 1⁄2 - >12 hours: given 2x or 1x/day (Ex.
Digoxin)
▪ By knowing the HALF-LIFE, the time it takes for
a drug to reach a steady state (plateau drug
level) can be determined.
▪ it can be achieved when the amount of drug
being administered is the same as the amount
of drug being eliminated.
▪ a steady state of drug concentration is
necessary to achieve optimal therapeutic
benefit.
EXCRETION
▪ Refers to the elimination of a drug from the
body
▪Most are excreted by the kidneys although
some are excreted in the bile then the feces
DRUG EXCRETION
▪ KIDNEYS – main route of drug excretion
▪ bile, lungs, saliva, sweat and breast milk.
▪ urine pH influences drug excretion.
▪ normal urine pH 4.6-8
▪ acidic urine promotes elimination of weak
base drugs.
▪ alkaline urine promotes elimination of weak
acid drugs.
▪ prerenal, intrarenal and postrenal conditions.