Equations/Useful_pharmacokinetic_equ_5127 1

Useful Pharmacokinetic Equations

Symbols

D =dose
t =dosing interval
CL =clearance
Vd =volume of distribution
k
e
=elimination rate constant
k
a
=absorption rate constant
F =fraction absorbed (bioavailability)
K
0
=infusion rate
T =duration of infusion
C =plasma concentration

General

Elimination rate constant
( ) ( )
k
CL
Vd
C
C
t t
C C
t t
e
= =
|
\

|
.
|

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