Beruflich Dokumente
Kultur Dokumente
K.PRADEEP KUMAR
M.PHARM (PHARMACEUTICS)
03-03-2011 1
CONTENTS
Ø Dosage regimen
Ø Drug accumulation
Ø Principle of superposition
Ø Multiple dosing with respect to I.V.
Ø Multiple dosing with respect to Oral route.
Ø Concept of loading dose, maintenance dose,
Ø References.
•
INTRODUCTION
• INTRODUCTION
A single dose may provide an effective
between doses.
1.
•
DRUG ACCUMULATION
A)Drug accumulation during multiple
dosing: following the 1st dose, if
the 2nd dose is given early enough
so that not the entire 1st dose is
eliminated then the drug will start
accumulating and we will get
higher concentration with the 2nd
and 3rd dose.
C ss max
Steady state
Plasma drug conc.
X0+1/2X0
Css min
X0+1/4 X0
1/2X0
Time[h]
8
No.of doses
no.of ½ 1 2 3 4 5 6 7 8
lives
0 100 max
1 50 min 150
2 75 175
3 87.5 187.5
4 93.8 193.88
5 96.88 196.88
6 98.44 198.44
7 99.22 192.22
8 99.6
10
•TheThe extent
extent toto which
which a drug
a drug accumulates
accumulates inin
thethe body
body is is a
a function
function
of its dosingofinterval
its dosing
andinterval and elimination
elimination of half-life
of half-life and is
and is independent
independent of dose size.
of dose size.
•
•The
The extent
extent toto which
which any
any drug
drug accumulate
accumulate with
with any
any dosing
dosing
interval
interval in ainpatient
a patient
cancanbe be derived
derived from
from information
information obtained
obtained
with a singlewith
dosea and
single dose and
is given is given by accumulation
by accumulation index Rac as :
index Rac as :
•
1
Rac = (1 – e-K Et)
Principle of superposition
accumulation t1/2 = t1/2 [1+3.3 log k /k -k]
a a
For iv administration, a is very rapid(approaches∞); k is
Accumulation t½ = elimination t½
12
Repetitive iv injection
On repeated drug administration,
the plasma concentration will be
added upon for each dose interval
giving a steady state
16
• The drug concentration in plasma at the end of
the second dosing interval is given by
C2Ʈ = C20 .e-K Ʈ = (C10r+C10)r (8)
Now this procedure can be used for finding zero time
concentration & drug concentration at the end of dosing
interval for each dose of the drug.
17
• Beginning= C10+C10r+C10r2+…………….+C10r(n-1)
(11)
• End = C10r+C10r2+C10r3+…………+C10rn (12)
• r<1, as n increases rn becomes smaller
• When n=∞ equation 11,12,becomes
• Cmax =C1/1-r= X0/Vd(1- e-KƮ ) (13)
• Cmin =Cmax .r
• An average study state concentration Cav is obtained by dividing
AUC for dosing period by the dosing interval
• Cav =[AUC]t2 t1 /Ʈ
• Plasma drug concenration at any time tCn=C0(1-e-nkƮ /1-e-kƮ ).e-kƮ
• N=no.of doses is time after nth dose. At steady state e-
nkƮ approaches zero ...C ∞=C (1/1-e-kƮ ) e-kƮ
n 0
18
Repetitive extra vascular dosing
20
Loading Dose
• A drug dose does not show therapeutic activity unless it
reaches the desired steady state.
• It takes about 4-5 half lives to attain it and therefore time taken
will be too long if the drug has a long half-life.
• Therapeutic effect can be reached immediately by
administering a dose that gives the desired steady state
instantaneously before the commencement of maintenance
dose X0.
• Such an initial or first dose intended to be therapeutic is called
as priming dose or loading dose.
•
Calculation Of Loading
I.V
Dose
Maintenance dose
X = X* (1-ekƮ )
0
Loading dose,
X* = X /(1-e-kƮ)
0
Dose ratio = X*/X0
22
Calculation Of Loading
Dose
• When T > t1/2 dose ratio is smaller than 2.0
• When T< t1/2 dose ratio is greater than 2.0
•
• If the loading dose is not optimum either too low or too high,
the steady state is attained within a 4-5 half lives in a
manner similar to when no loading dose is given.
23
Dose ratio >2
Dose ratio 2
MSC
Cp
MEC
24
Conclusion
25
Reference
26
THANK YOU
27