DOSAGE REGIMENS

DOSE:

Quantity of a drug given to the patient at

one time to produce certain therapeutic
effect.
DIFFERENT DOSES:

MAINTENANCE DOSE
LOADING DOSE
PEDIATRIC DOSE
EFFECTIVE DOSE
MEDIAN EFFECTIVE DOSE
LETHAL DOSE
MEDIAN LETHAL DOSE

MAINTENANCE DOSE:
In most clinical conditions, drugs are
administered in a series of repetitive doses
or as a continuous infusion in order to
maintain a steady state concentration of the
drug in the body i.e. just enough drug is
given in each dose to replace the drug

eliminated since the preceding dose.

Therefore calculation of maintenance dose is
essential.
To maintain a chosen target concentration
(Css), rate
of drug input (maintenance dose) is equal to
rate of
drug clearance.
Dosing Rate = Rate of clearance at specified
target
concentration.
Dosing rate (I/V) = Cl TC (Target
Concentration)

If the desired target concentration is known,

clearance of drug will determine dosing rate.
If the drug is given by route that has
bioavailability less than 100% (oral route)
dosing rate is predicted by

Dosing rate (oral) = dosing rate (I/V)

F (oral)
F is the bioavailability

OR
Dosing rate = Cl TC
F
If intermittent doses are given maintenance
dose is calculated as
Maintenance dose = Dosing rate Dosing
interval.

LOADING DOSE:
Loading dose is one or series of doses
that may
be given at onset of therapy to achieve
target
concentration quickly, it is calculated as
Loading dose = TC Vd
F
Loading dose may be desirable if time
required
to attain steady state concentration by
the
administration of drug at constant rate is
long

relative to demands of the condition

being
treated.

Disadvantages of loading dose:

Patient may be exposed abruptly to

toxic concentration of a drug.

If drug has long half-life, it will take
long time for the concentration to fall, if
plasma level of drug is high.
Loading dose is usually given
intravenously, this is particularly
dangerous if loading dose is large and
drug is administered rapidly.

PEDIATRIC DOSE:

Because of the differences in

pharmacokinetics in infants and children,
they require small doses as compared to
adults.
The approximation of pediatric doses can
be made by methods based on age, weight

and surface area.

These approximations are not precise and
should not be used if manufacturer
provides a pediatric dose.
YOUNGS RULE:
Pediatric dose = Age of child adult
dose
Age + 12

FRIED RULE:
Pediatric dose = Age (in months) adult
dose
150
CLARKS RULE:
Pediatric dose = Weight (in Kg) adult
dose
70
Pediatric dose = Weight (in Lbs) adult
dose
150
Based on surface area:
Pediatric dose = Surface area (in sq. m)
adult dose

1.7
Dosage calculation based on surface area is
more appropriate than age and body weight.

Determination of Drug Dose

Calculate Body Surface Area
Height (cm) x Weight (kg)
3600

THERAPEUTIC INDEX

It is the ratio of median lethal dose (LD50) to

median effective dose (ED50). OR It is the
measurement that describes the relationship
between doses of drugs required to produce
undesired and desired effects.
T I = LD50
ED50
Median lethal dose is the minimum amount of
drug in mg/Kg body weight that kills 50% of
test animals.

Median effective dose is the minimum amount

of drug in mg/Kg body weight that produces
desired effects in 50% of test animals.
ED50 is the measure of potency of the drug,
lower the dose more potent is drug and vice
versa.

STANDARD MARGIN OF SAFETY:

When Therapeutic index may be misleading,

Standard margin of safety may be more
useful.
Standard margin of safety shows the
percentage by which ED99 (Dose effective in
99% of population) must be increased to
cause toxic effects in 1% of population.
Formula for standard margin of safety
(SMS)is:
LD1 x 100
ED99
Therapeutic Index
TD50/ED50

Dose-Response Function
ED50
Dose-Response Function
TD5o
Dose-Response Function
LD50
Dose-Response Function
ED50 ,TD50 ,LD50

EFFICACY:

Maximal effect that can be elicited by a drug is

called efficacy, it is measured by Emax.
Efficacy is more important than potency in
selecting drug for clinical use.

POTENCY:

Concentration (EC50) or dose (ED50) of a drug

that produces 50% of the maximal effect of
that drug is called potency, lower the ED50
more potent is the drug.

Efficacy & Potency

Efficacy & Potency

Efficacy & Potency
Summation

Potentiation
DOSE RESPONSE
RELATIONSHIP

Two basic types of dose response

relationships have been observed,
these are:
1. QUANTAL OR ALL & NONE DOSE
RESPONSE RELATIONSHIP:
In this type of relationship a single
dose of the drug either produces no
effect or produces maximum effect.

DOSE RESPONSE
RELATIONSHIP
GRADED OR QUANTITIVE DOSE
RESPONSE RELATIONSHIP:

In this type of relationship as the dose

administered to a single subject is increased,

the pharmacological response also increases

in a gradual fashion.
The degree of effect produced by increasing
the dose of drug eventually reaches steady
level. This phenomenon is called ceiling effect
and dose at which it occurs is called ceiling
dose.
Increasing the dose beyond this dose
produces undesirable effect.

OTHER DRUG THERAPY:

Drugs may modify the response to each

other by pharmacokinetic or
pharmacodynamics interaction
between them.
Drug interaction does not necessarily
mean that their concurrent use is
contraindicated; many drugs can be
used beneficially and some with dose
adjustment.
Drug combinations can produce:
Additive effect.

Synergism.
Potentiation.
Antagonism.