Multiple IV bolus

dosing, concept
of accumulation,
fluctuation and
steady state level

From, POONAM PATIL 1

 Dosage
Regimen
Dosage regimen is defined as the
manner in which drug is taken.

For some drugs like analgesic,

hypnotics, antiemetic, etc. a single
dose may provide effective treatment.

However, the duration of most illnesses

is longer than the therapeutic effect
produced by single dose. In such cases,
drugs are required to be taken on
repetitive basis over a period of time
depending upon the nature of illness.
Thus for successful therapy, design of
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 Multiple dosage regimen

An optimal multiple dosage form is

the one in which the drug is
administered in suitable doses (by a
suitable route), with sufficient
frequency that ensures maintains of
plasma concentration within the
therapeutic window ( without
excessive fluctuation and drug
accumulation) for the entire duration
of therapy.

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Dose
size

The magnitude of both therapeutic

and toxic responses depends upon the
dose size.

Greater the dose size, greater the

fluctuations between Css,max and
Css,min during each dosing interval
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Dosing
frequency

Dosing frequency is calculated on the

basis of half-life of drug. If the interval
is increased and dose is unchanged,
Cmax, Cmin and Cav decrease but the
ratio Cmax / Cmin increases. Opposite is
observed when dosing interval is
reduced or dosing frequency
increased.It also results in greater drug
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 LOADING DOSE

A drug does not show therapeutic

activity unless it reaches the
desired steady-state. It takes about
5 half lives to attain it and
therefore the time taken will too
long if the drug has long half-life.
Plateau can be reached
immediately by administrating a
dose that gives the desired steady
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 In situation to attain plasma
concentration rapidly it is
necessary to give loading dose in
beginning.

 Single large dose of series of

quickly repeated doses given to
rapidly attain target concentration.

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 Maintenance dose

Dose of drug which is repeated at

specific interval to maintain plasma
steady state level.

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 FLUCTUATIONS
It is defined as ratio of Cmax / Tmax

Greater the ratio greater the

fluctuations like accumulation, it
depend upon dosing frequency and
half life of the drug.
It also depends upon the rate of
absorption.

The greatest fluctuations is observed

when drug is given extravascularly
because of continuous absorption.

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 Accumulation

It occurs because drug from previous

dose has not been removed
completely.

It is simply reflection of how much

drug is being added to the body
relative to how much is being
eliminated from the body during a
defined period of time and that ratio
can be controlled by changing the
dosing frequency.

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