This document discusses the concepts of loading and maintenance doses for drugs. It defines a loading dose as a larger initial dose used to quickly attain the steady-state drug concentration in plasma. The size of the loading dose depends on the maintenance dose, elimination rate constant, and dosing interval. It also discusses how to calculate loading doses based on either the maximum or minimum steady-state plasma concentration. After the loading dose, maintenance doses are given to maintain the steady-state concentration over the dosing interval. Factors like therapeutic index and drug half-life also impact maintaining concentrations within the therapeutic window.

1. CONCEPT OF LOADING AND
MAINTENANCE DOSE
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2. CONTENT
 INTRODUCTION
 DEFINITION
 CONCEPT
 FACTORS
 REFERENCE
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3. 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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4.  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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5.  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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6. 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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7.  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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8. 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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9. 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)
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10.  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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11.  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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12.  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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13.  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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14. 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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15.  When a single bolus dose of the drug
is administered intravenously
 Therefore
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16.  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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17.  Common terms canceled
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18. 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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19. 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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20. 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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21.  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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22. 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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23.  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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24.  Since the y-intercept,Cmin1 is directly
proportional to D
 If D is administered at the first dose
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25.  When Cmin1=Cminss
 Substituting the values
 Bringing RHS of eq to common
denominator
 Upon simplification
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26.  Dividing both side by (e-p – e-G)
 Cancelling common term
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27. 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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28.  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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30. 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
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31. REFERENCE
 Madan PL;Biopharmaceutics and
pharmacokinetics. Jaypee.2010(1);365-80.
 Brahmankar DM, Sunil Jaiswal B;
Biopharmaceutics and Pharmacokinetics-
A Treatise. Vallabh publication. 2014(3);
374-76.
 C V S Subrahmanyam. Textbook of
Biopharmaceutics & pharmacokinetics.1st
edition 2010;456-61.
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