loading dose and maintainance dose.power point(pptx)

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The CONCEPT OF LOADING
AND MAINTENANCE DOSE
DR KAWALYA STEVEN
Victoria university kampala

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INTRODUCTION
• Most drugs for chronic condition are prescribed in a dosage regimen
is based on the administration of a fixed constant dose(D) at fixed
regular dosing intervals(T) for long period of time.
• The D & T recommended by the manufacturer is based on the
effective therapeutic concentration of drug in the plasma needed to
treat the chronic condition.

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• The T is based on elimination rate constant of the drug.
• The steady-state concentration of drug in plasma during multiple
dosing is given by following equation:

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• The concentration of drug in plasma at steady-state depends on
the following 3 factors:
a) C0, concentration of drug in plasma.
b) Ke, elimination rate constant.
c) T, the dosing interval.

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DEFINITION & CONCEPT
• Loading dose: A dose of medication, often larger than subsequent
doses, administered for the purpose of establishing a therapeutic level
of the medication.
• Primary purpose of using loading dose in therapeutic treatment is to
attain steady-state concentration of the drug as quickly as possible,
usually right from the start of the dosage regimen for the treatment.

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• This approach may also reduce the time of onset of drug action,
i.e; the time its takes to achieve the minimum effective
concentration.
• The purpose of administering the loading dose is to reduce the
time needed for the drug to accumulate to the steady-state level
in the plasma.
• The size of loading dose will depend on the T of the maintenance
dose.

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INTRAVENOUS ADMINISTRATION
• A drug when administered intravenously as a single rapid bolus dose,
confers the characteristics of one-compartment model on the body.
• The main purpose of loading dose(D*) is to provide a steady-state
concentration in plasma during multiple dosing.

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Loading dose based on Cmax ss
• The max concentration of drug in the plasma at steady-state, Cmax ss is
given by equation
C0 is plasma concentration immediately after administration of a single
dose.
e-p
is persistence factor where P=(Ke) (T)

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• If the drug follows linear pharmacokinetics then C0 obtained after
the administration of single i.v rapid bolus dose is directly
proportional to size of dose D(maintenance dose).
• The max concentration at steady-state is

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• Concentration of drug in plasma immediately after administration
of the first dose is given by
• Vd= apparent volume of distribution
• therefore

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• The max conc after the first dose is
• Since Cmax 1 = Cmaxss, the conc *C0 of drug in plasma immediately
after (D*) is given by
*C0 = Cmaxss
• Substuting *C0 and Cmaxss gives

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• The size of loading dose depends on the following factors-
a) Maintenance dose ,D
b) Elimination rate constant , Ke
c) Dosing interval ,T.

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Loading dose based on Cmin ss
• The minimum concentration of drug in plasma at steady-state is
given by equation
• If drug follows linear p’kinetics then C0 is directly proportional to
size of D
• The min concentration of drug in plasma at steady-state is

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• When a single bolus dose of the drug is administered
intravenously
• Therefore

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• The min conc of drug in plasma after administration of first dose
• For D* Cmin 1 = (*C0 ) (e-p
),which should be equal to Cmin ss
• Combining eq

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• Common terms canceled

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Factors affecting size of dose
• If all doses and all T are kept constant, then the size of D depends on
size of D*, T & Ke
Effect of dosing interval:
• If the size of D is kept constant & biological halflife of the drug dose
not change during the course of therapy, the size of D* depends
entirely upon the T of a given drug.

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EXTRAVASCULAR ADMINISTRATION
• For the determination of D* during e.v, administration, the simplest
case is a drug which, when administered, confers upon the body the
characteristics of one-compartment model, & does not exhibit lag-
time.
• The size of D* needed to attain steady-sate conc of drug in plasma
depends on:

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a. Maximum concentration of drug in plasma at steady state.
OR
b. Minimum concentration of drug in plasma at steady state.
LOADING DOSE BASED ON Cmaxss
• The maximum concn of drug in plasma at steady-state is given
by

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• Where B is the back extrapolated y-intercept of the elimination
phase after administration of a single dose.
• R=(Ke) (tmax)

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Loading dose based on Cmin ss
• The minimum conc of drug in plasma following e.v adminstration of n
dose
• If the drug follows linear pharmacokinetics then B
• F=fraction of dose absorbed
• G= (Ka)( T)

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• By setting n=1 in above eq in Cmin1
• Canceling common terms
• When n becomes large, the two exponential terms e-np
e-nG
approach 0

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• Since the y-intercept,Cmin1 is directly proportional to D
• If D is administered at the first dose

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• When Cmin1=Cminss
• Substituting the values
• Bringing RHS of eq to common denominator
• Upon simplification

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• Dividing both side by (e-p
– e-G
)
• Cancelling common term

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Maintenance Dose
• After the loading dose is given the another dose is given to maintain
the steady- state drug conc. / plateau. Such dose is known as
maintenance dose.
• i.e. maintain the response of drug by replacing drug lost during
dosing interval

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• Maintenance dose = loading dose . ( 1- e k‫ז‬
)
• Loading dose =
• The ratio of loading dose to maintenance dose (X0l/X0) is called as dose ratio
• When ‫ז‬ = t1/2 the dose ratio =2.0
• When ‫ז‬ > t1/2 the dose ratio < 2.0
• when ‫ז‬ < t1/2 the dose ratio >2.0

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Maintenance of drug within the therapeutic
range
The ease or difficulty in maintaining drug concentration within the
therapeutic window depends on-
• The Therapeutic index of drug
• The Half- life of drug
• Convenience of dosing

loading dose and maintainance dose.power point(pptx)

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