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PKinetics-IVbolus

PKinetics-IVbolus

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Published by Sougata Pramanick
Banakar pharmacokinetics
Banakar pharmacokinetics

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Published by: Sougata Pramanick on Jun 08, 2008
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 Basic PharmacokineticsREV. 00.1.2
4-1
Copyright © 1996-2000 Michael C. Makoid All Rights Reservedhttp://pharmacy.creighton.edu/pha443/pdf 
CHAPTER 4
 I.V. Bolus Dosing
 Author: Michael Makoid and John Cobby Reviewer: Phillip Vuchetich
O
 BJECTIVES
For an IV one compartment model plasma and urine:
1.Given patient drug and/or metabolite concentration, amount, and/or rate vs. timeprofiles, the student will calculate (III) the relevant pharmacokinetic parametersavailable from IV plasma, urine or other excreta data: e.g.2.The student will provide professional communication regarding the pharmacoki-netic parameters obtained to patients and other health professionals.3.The student will be able to utilize computer programs for simulations and dataanalysis.
K
m
 AUCAUMCCLMRT
12
 ⁄ 
,,,,, , , ,
 
I.V. Bolus Dosing
 Basic PharmacokineticsREV. 00.1.2
4-2
Copyright © 1996-2000 Michael C. Makoid All Rights Reservedhttp://pharmacy.creighton.edu/pha443/pdf 
4.1I.V. Bolus dosing of Parent compoun
4.1.1PLASMA
Valid equations:(Obtained from theLaPlace transformsderived from theappropriate modelsderived from thepharmacokineticdescriptions of the drug)
(EQ 4-1)(EQ 4-2)(EQ 4-3)(EQ 4-4)(EQ 4-5)(EQ 4-6)(EQ 4-7)(EQ 4-8)(EQ 4-9)
Utilization:
Can you determine theslope and intercept froma graph? Plot the datain table 4 -1.on semi-loggraph paper. Extrapo-late the line back to time= 0 to get Cp
0
. Find thehalf life. Calculate theelimination rate con-stant.
You should be able to plot a data set Concentration vs. time on semilog yielding a straight linewith slope = and an intercept of .
FIGURE 4-1.
 p
ln
Kt
 p
0
ln+
=
 X 
ln
Kt
0
ln+
=
 p
 p
0
e
Kt 
=
 p
0
 D
------=
½
0.693
-------------=
 AUCCpt 
0
( )
∫ 
=
Σ
Cp
n
Cp
n
1+
+
( )
2-------------------------------------
  
Cp
last 
--------------+=
 AUMCt
 p
n
Cp
n
( )
n
1+
Cp
n
1+
( )
+2--------------------------------------------------------------------
  
0
Cp
last 
2
---------------
last 
Cp
last 
( )
----------------------------------++=
0
( )
∫ 
=
 MRT  AUMC  AUC 
------------------=
ClKV 
=
TABLE 4-1
Nifedipine 25 mg IV bolus
Time (hr)Cp(mcg/L)
21394 65.66 31.18 14.6
 p
0
 
I.V. Bolus Dosing
 Basic PharmacokineticsREV. 00.1.2
4-3
Copyright © 1996-2000 Michael C. Makoid All Rights Reservedhttp://pharmacy.creighton.edu/pha443/pdf 
Does your Graph looklike this?
FIGURE 4-1
Nifedipine IV Bolus (25 mg IV Bolus)
You should be able to determine K. A plot of the data inTABLE 4-1results inFIGURE 4-1 Remember from high school algebra, the slope of any straight line is the rise over the run, ,In the case of semi-log graphs
y is the difference in the logarithms of the concentrations. Thus,using the rules of logarithms, when two logs are subtracted, the numbers themselves aredivided. i.e. . Thus if we are judicious in the concentrations that wetake, we can set the rise to a constant number. So, if we take any two concentrations such thatone concentration is half of the other (InFIGURE 4-1above, we took 100 and 50), the time ittakes for the concentration to halve is the half life (in the graph above, 1.85 hr). Then
You should be able to determine :. To do this, extrapolate the line to . The value of when is (in the graph above, which is equal to for an IV bolusdose only.Thus,The volume of distribution is a mathematical construct. It is merely the proportionality constantbetween two knowns - the which results from a given . It is, however, useful because itis patient specific and therefore can be used to predict how the patient will treat a subsequentdose of the same drug. You should be able to obtain the volume of distribution from graphicalanalysis of the data. Pay attention to the units! Make sure that they are consistent on both sidesof the equation. NOTE: the volume of distribution is not necessarily any physiological space.For example the approximate volume of distribution of digoxin is about 600 L If that were aphysiological space and I were all water, that would mean that I would weigh about 1320pounds. I’m a little overweight (I prefer to think that I’m underheight), but REALLY!
Given any three of the variables of the IV bolus equation, either by direct information (the vol-ume of distribution is such and such) or by graphical data analysis, you should be able to findthe fourth.
02468
Time (hours)
10
1
10
2
10
3
   C  o  n  c  e  n   t  r  a   t   i  o  n   (  n  g   /  m   L   )
 
-K1 = -0.375 hr
-1
C
p0
= 295 mic/L
 
 
   C  o  n  c  e  n   t  r  a   t   i  o  n   (  m   i  c   /   L   )
Time (hr)
1.85 hr
10050
y
x------
1
( )
ln
2
( )
ln
1
2-------
  
ln=
0.693
½
-------------0.6931.85
hr 
----------------0.375 hr
1
===
0=
 p
0=
 p
0
 p
0
295
mic L
---------=
 D
 ⁄ 
Cp
0
 Dose
------------- 
 DoseCp
0
-------------25
mg
295
mic L
------------------------------------=1000
micmg
---------------------85
 L
=
=,=
 p
0
 D
0

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