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III. Drug Metabolism
 The
aim
of
drug
metabolism is to convert
lipid soluble (non polar)
drugs to polar metabolites
easily excreted in urine.
 The liver is the principle
organ of drug metabolism.
The drug metabolite may be:
Inactive: metabolism results in termination of drug
action e.g. most drugs.
Active like the parent drug: e.g. diazepam (sedative
and hypnotic).
Active and the parent drug is inactive: (prodrug)
e.g. methotrexate
IV. Drug Excretion
 Kidney is the major rout of
excretion of drugs or their
metabolites.
 Other
channels
of
excretion include the lungs,
intestine, skin and milk.
 Drugs are eliminated from
the body either unchanged
as the parent drug or as
metabolites (a changed form
of the drug).
 Since drugs are small particles dissolved in the blood,
they are usually filtered into the kidneys and then
reabsorbed back into the bloodstream.
 In order for the kidney to eliminate drugs from the
body, the drug must somehow be prevented from
being
reabsorbed
from
the
urine
into
the
bloodstream.
 The drug must be chemically changed into a
compound that is less fat-soluble and therefore less
capable of being reabsorbed.
Drug Product (Delivery system):
The dosage form that contains the therapeutically
active agent (s), generally but not necessarily in
association with inactive ingredients (e.g. tablet,
capsule, suspension, ….. ).
Drug product selection:
The process of selecting dosage form in which the
drug product will be manufactured.
The duration of drug therapy:
The time necessary for the treatment of a disease
with a drug.
Dosage regimen:
 Is the manner in which a drug is taken.
 It comprises calculation of the required dose (size
of the dose) and adjusting dosing interval (dosing
frequency) for patients.
Therapeutic Objective:
 It may be either the treatment, mitigation or the
prevention of the disease.
 It is evident that both the duration of drug
therapy and the dosage regimen depend on the
therapeutic objective.
Minimum Effective Concentration (MEC):
 Many drugs have no demonstrable therapeutic
effect or do not produce a desired degree of
pharmacologic response unless a minimum
concentration is reached at the receptors (sites of
action).
 The MEC represents the minimum concentration
of a drug needed at the sites of action (receptors)
to produce the desired pharmacologic effect.
Minimum Toxic Concentration (MTC):
conc.
It reflects the drug
concentration
at
Toxic
MTC
which a toxic effect
will appear.
Therapeutic
MEC
Ineffective
time
Therapeutic concentration range
(Therapeutic window):
 It is the range of drug concentration between the
MEC and the MTC.
 In other words, it is a region associated with
therapeutic effect.
 An optimal dosage regimen might be defined as
one that maintains the plasma concentration of a
drug within its therapeutic window.
Drug with narrow therapeutic window:
 These drugs require
conc.
Therapeutic drug
Toxic
concentration monitoring.
 Examples:
Therapeutic Window
e.g.1 Digoxin
e.g.2 Warferin
e.g.3 Theophylline
Ineffective
time
Therapeutic effectiveness:
 Is the difference between effective therapy and
toxic effects.
Biopharmaceutics:
 Is
the study of the effect of various
pharmaceutical formulation variables on the
delivery of the drug to the body under normal and
pathologic conditions (impaired physiological
function).
Bioavailability:
 Is the rate (amount/time) and extent (total
amount) to which the active drug ingredient or
therapeutic moiety is absorbed from a drug
product and becomes available at the receptor
(site of action).
 When a medication is administered intravenously,
its bioavailability is 100%.
 However when a medication is administered via
other routes (orally), its bioavailability generally
decreases (due to incomplete absorption and firstpass metabolism) or may vary from patient to
patient.
 Bioavailability
must
be
considered
when
calculating dosages for non-intravenous routes of
administration.
Pharmaceutic equivalents:
 These are drug products that are identical in:
 Active drug ingredient
 Strength or concentration
 Dosage form
 Route of administration
 They may differ in some characteristics e.g.
colour, shape, packing, expiration time and
inactive ingredients.
Bioequivalent drug products:
 These are pharmaceutical equivalents whose rate
and extent of absorption are not different (i.e.
have similar bioavailability).
 When given in the same concentration (molar
dose) under similar experimental conditions).
Pharmaceutic alternatives:
 These are drug products that contain the same
therapeutic moiety but not necessarily as the
same chemical structure.
e.g.1 Betamethasone Acetate and Betamethasone
Valerate
e.g.2 Tetracyclin Hydrochloride and Tetracyclin
Phosphate
 Also, different dosage forms containing the same
active ingredients and produced by a single
manufacturer are pharmaceutic alternatives.
e.g.1 Sustained-release dosage form (Olfen SR)R
versus
a
standard
immediate-release
drug
product of the same ingredient (Olfen)R.
e.g.2 Diclofenac Sodium (Declophen)R ampoule
and Diclofenac Sodium (Declophen)R tablet.