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|
.
|
ln
ln ln
1
2
2 1
1 2
2 1
Half-life
t
Vd
CL k k
e e
1 2
0693 2 0693
/
. ln( ) .
=
= =
Intravenous bolus
Initial concentration
C
D
Vd
0
=
Plasma concentration (single dose)
C C e
k t
e
=
0
Plasma concentration (multiple dose)
( )
C
C e
e
k t
k
e
e
=
0
1
t
Peak (multiple dose)
( )
C
C
e
k
e
max
=
0
1
t
Trough (multiple dose)
( )
C
C e
e
k
k
e
e
min
=
0
1
t
t
Average concentration (steady state)
Cp
D
CL
ss
=
t
Oral administration
Plasma concentration (single dose)
( )
( )
C
F D k
Vd k k
e e
a
a e
k t k t
e a
=
Time of maximum concentration (single
dose)
( )
t
k
k
k k
a
e
a e
max
ln
=
|
\
|
.
|
Plasma concentration (multiple dose)
( )
( ) ( )
C
F D k
Vd k k
e
e
e
e
a
a e
k t
k
k t
k
e
e
a
a
=
|
\
|
.
|
|
1 1
t t
Time of maximum concentration (multiple
dose)
( )
( )
( )
t
k e
k e
k k
a
k
e
k
a e
e
a
max
ln
=
|
\
|
.
|
|
1
1
t
t
Average concentration (steady state)
C
F D
CL
=
t
Clearance
AUC
F Dose
Cl
=
d e
V k Cl =
Equations/Useful_pharmacokinetic_equ_5127 2
Constant rate infusion
Plasma concentration (during infusion)
( )
C
k
CL
e
k t
e
=
0
1
Plasma concentration (steady state)
C
k
CL
=
0
Calculated clearance (Chiou equation)
( )
( )
( ) ( )
CL
k
C C
Vd C C
C C t t
=
+
+
+
2 2
0
1 2
1 2
1 2 2 1
Short-term infusion
Peak (single dose)
( )
C
D
CL T
e
k T
e
max( ) 1
1 =
Trough (single dose)
( )
C C e
k T
e
min( ) max( ) 1 1
=
t
Peak (multiple dose)
( )
( )
C
D
CL T
e
e
k T
k
e
e
max
=
1
1
t
Trough (multiple dose)
( )
C C e
k T
e
min max
=
t
Calculated elimination rate constant
k
C
C
t
e
=
|
\
|
.
|
-
-
ln
max
min
A
with C
max
*
=measured peak and C
min
*
=
measured trough,
measured over the time interval At
Calculated peak
C
C
e
k t
e
max
max
=
-
-
with C
max
*
=measured peak, measured at time
t
*
after the end of the infusion
Calculated trough
C C e
k t
e
min min
=
-
-
with C
min
*
=measured trough, measured at
time t
*
before the start of the next infusion
Calculated volume of distribution
( )
)] ( [
1
min max
T
e
k
T
e
k
e e C C
e
T k
D
Vd
=
Calculated recommended dosing interval
t =
|
\
|
.
|
+
ln
max( )
min( )
C
C
k
T
desired
desired
e
Calculated recommended dose
( )
( )
D C k V T
e
e
desired e
k
k T
e
e
=
max( )
1
1
t
Two-Compartment-Body Model
C a e b e
t t
= - + -
o |
AUC a b
= + / / o |
Vd Vd Vc
area ss
> >
Creatinine Clearance
CL male
age weight
Cp
creat
creat
( )
( )
=
-
-
140
72
CL female
age weight
Cp
creat
creat
( )
( )
=
-
-
140
85
With weight in kg, age in years, creatinine plasma conc.
in mg/dl and CL
creat
in ml/min
Equations/Useful_pharmacokinetic_equ_5127 3
K
e
for aminoglycosides
K
e
=0.00293(CrCL) +0.014
Metabolic and Renal Clearance
E
H
=
Cl fu
Q Cl fu
b
H b
int
int
+
Cl
H
= E Q
H H
=
Q Cl fu
Q Cl fu
H b
H b
+
int
int
F
H
=
b H
H
fu Cl Q
Q
+
int
Cl
ren
= RBFE =
in
out in
C
C C
GFR
Cl
ren
=
ion concentrat plasma
excretion of rate
Cl
ren
=
(
+
ion concentrat Plasma
on reabsorpti of Rate - secretion of Rate
GFR fu
Cl
ren
=
ion concentrat Plasma
ion concentrat urine flow Urine
Ideal Body Weight
Male
IBW =50 kg +2.3 kg for each inch over 5ft in
height
Female
IBW =45.5 kg +2.3 kg for each inch over 5ft in
height
Obese
ABW =IBW +0.4*(TBW-IBW)
Volume of Distribution
P T P
K V V V + =
T
T P
fu
fu
V V V + =
Clearance
AUC
Dose
Cl =
d e
V k Cl =
Last modified 2010
C:\Current Data\pha5127_Dose_Opt_I\equations\5127-28-equations.doc
For One Compartment Body Model
If the dosing
involves the use
of I.V. bolus
administration:
For a single I.V. bolus administration:
V
D
C =
0
t k
e
e C C
=
0
For multiple I.V. bolus administration:
( )
( )
t k
k
nk
e
e
e
e
e
e
V
D
t Cn
=
t
t
1
1
) (
at peak: t =0; at steady state n
at trough: t =t
) e (
V
D
C
e
k
ss
t
=
1
1
max
t
e
k
ss ss
e C C
=
max min
If the dosing
involves the use
of I.V. infusion:
For a single short-term I.V. infusion:
Since t =t for C
max
( )
T k
e
e
e
T Vk
D
C
= 1
max
) (
max min
T k
e
e C C
=
t
For multiple short-term I.V. infusion at steady state:
( )
( )
t
e
e
k
T k
e e
e
T Vk
D
C
=
1
1
max
) (
max min
T k
e
e C C
=
t
Last modified 2010
C:\Current Data\pha5127_Dose_Opt_I\equations\5127-28-equations.doc
If the dosing
involves a I.V.
infusion (more
equations):
( )
t k T k
e
t
e e
e e
T Vk
D
C
= 1 (most general eq.) during infusion t =T so,
( )
t k
e
t
e
e
T Vk
D
C
= 1 (during infusion) at steady state t , e
-k
e
t
,
t 0 so,
CL
k
Vk
k
T Vk
D
Cpss
e e
0 0
= = = (steady state) remembering
T
D
k =
0
and
e
k V CL =
If the dosing
involves oral
administration:
For a single oral dose:
( )
( )
t k t k
e a
a
a e
e e
k k V
k D F
C
=
( )
e a e
a
k k k
k
t
=
1
ln
max
For multiple oral doses:
( )
( ) (
t
a
a
e
e
k
t k
k
t k
e a
a
e
e
e
e
k k V
k D F
C
1 1
( )
( )
( )
e a
k
e
k
a
k k
e k
e k
t
a
e
(
(
1
1
1
ln
max
t
t