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PKinetics-IVinfsn

PKinetics-IVinfsn

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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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05/09/2014

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 Basic PharmacokineticsREV. 99.4.25
5-1
Copyright © 1996-1999 Michael C. Makoid All Rights Reservedhttp://kiwi.creighton.edu/pkinbook/ 
CHAPTER 5
 I.V. Infusion
 Author: Michael Makoid and John Cobby Reviewer: Phillip Vuchetich
O
 BJECTIVES
1.Given patient drug concentration and/or amount vs. time profiles, the student willcalculate (III) the relevant pharmacokinetic parameters available (, K, , ,, Clearance, MRT) from IV infusion data.2.I.V. Infusion dosing for parent compounds3.Plasma concentration vs. time profile analysis4.Rate vs. time profile analysis5.Professional communication of IV Infusion information6.Computer aided instruction and simulation7.Metabolite (active vs. inactive)
m
 AUC 
 
I.V. Infusion
 Basic PharmacokineticsREV. 99.4.25
5-2
Copyright © 1996-1999 Michael C. Makoid All Rights Reservedhttp://kiwi.creighton.edu/pkinbook/ 
5.1Parent compoun
5.1.1PLASMA
Valid equations:
or
(EQ 5-1)(EQ 5-2)
at any time during the infusion 
(EQ 5-3)
at steady state (t is long) 
(EQ 5-4)
after termination of infusion
Where is the plasma concentrationis the infusion rate shown in equation 5-1 and equation 5-2.is the plasma concentration when theinfusion is stopped.Rewriting equation 5-4 to an equation which may be used by a computer results in:
(EQ 5-5)
whereand .
 p
QK
--------------1
e
Kt 
( )
=
 p
 DoseK
infusion
--------------------------------------- 1
e
Kt 
( )
=
 p
( )
ss
QK
--------------=
 p
 pterm
( )
e
Kt 
=
 p
Q Dose
infusion
-------------------=
 pterm
( )
QK
--------------1
e
Kt 
infusion
( )
=
CpQK
------------
e
e
( )
=
T
iv
( )
=for
T
iv
>( )
0=for
T
iv
<( )
 
I.V. Infusion
 Basic PharmacokineticsREV. 99.4.25
5-3
Copyright © 1996-1999 Michael C. Makoid All Rights Reservedhttp://kiwi.creighton.edu/pkinbook/ 
Using The Scientist
@
‘s Unit function makes the change in straight forward. InThe Scientist
@
, Unit(+) = 1 and Unit(-) = 0, so definingmeets these needs.This equation is utilized in The Scientist
@
’s companion product PKAnalyst
@
alsoby MicroMath. Since the route of administration is an infusion and we wouldknow how much we gave (
 Dose
), how fast we gave it (
Q
), and over how long theinfusion lasted (
iv
), the only other variables in the equation are
and
. PKAn-alyst asks for
iv
and yields
 DoverV 
( ) and
as parameters resulting fromnon-linear regression analysis. Dividing
 Dose
by yields
.
Utilization:
You should be able to determine the infusion rate necessary to obtain a desiredplasma concentration. Rearranging equation 5-3 results in:
 
(EQ 5-6)
You should be able to determine how long it would take to get to a desired plasmaconcentration. Using equation 5-1 and equation 5-3, it looks like it will take for-ever to get exactly to steady state because in order for, which occurs when . So,how close is close enough? If , that’s good enough in mostpeople’s estimation. So in order to find out how long it will take we use equation5-1, setting and solve for time. Thus:which results in 
T
iv
( )
UNIT
T
iv
( )
=
 Dose
-------------
 Dose
-------------
K
 p
( )
ss
Q
=
 p
( )
ss
QK
--------------
QK
--------------1
e
Kt 
( )
==
e
Kt 
0
=
 p
( )
0.95
 p
( )
ss
=
 p
( )
0.95
 p
( )
ss
=
 p
( )
0.95
 p
( )
ss
QK
--------------1
e
Kt 
( )
==0.951
e
Kt 
( )
=0.951
e
Kt 
=ln 0.05
( )
Kt 
=2.996
Kt 
=

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