Useful Pharmacokinetic Equations

Symbols Trough (multiple dose)

C e k e
C min 0 k
D = dose
1 e e
= dosing interval
CL = clearance
Average concentration (steady state)
Vd = volume of distribution
D
ke = elimination rate constant Cp ss
ka = absorption rate constant CL
F = fraction absorbed (bioavailability)
K0 = infusion rate
T = duration of infusion Oral administration
C = plasma concentration
Plasma concentration (single dose)
F D ka
General C
Vd k a k e

e k e t e k a t
Elimination rate constant
C Time of maximum concentration (single
ln 1
CL C 2 ln C1 ln C 2 dose)
ke
Vd t 2 t1 t 2 t1 k
ln a
ke
t max
Half-life ka k e
0.693 Vd ln( 2 ) 0.693
t1 / 2
CL ke ke Plasma concentration (multiple dose)
F D ka e k e t e k a t
C
Intravenous bolus
Vd k a k e 1 e k e
1 e k a

Initial concentration Time of maximum concentration (multiple

D dose)
C0
Vd
k a 1 e k e
ln

t max
e
k 1 e k a

Plasma concentration (single dose)
C C 0 e k e t
ka k e

Plasma concentration (multiple dose) Average concentration (steady state)

F D
C e k e t C
C 0 k CL

1 e e
Clearance
Peak (multiple dose) Dose F
C0 Cl
C max AUC

1 e k e
Cl ke Vd

Equations/Useful_pharmacokinetic_equ_5127 1
Constant rate infusion Calculated peak
C
C max kmaxt
Plasma concentration (during infusion) e e
k

C 0 1 e k e t
CL
with Cmax* = measured peak, measured at time
t* after the end of the infusion

Plasma concentration (steady state) Calculated trough

k C min C min e k e t
C 0
CL
with Cmin* = measured trough, measured at
Calculated clearance (Chiou equation) time t* before the start of the next infusion
2 k0 2 Vd C1 C 2
CL
C1 C 2 C1 C 2 t 2 t1 Calculated volume of distribution

Vd
D

1 e k e T
Short-term infusion k e T [C k e T
max (C min e )]
Peak (single dose)
Calculated recommended dosing interval
C max(1)
D
CL T

1 e k e T
C max(desired )
ln
Trough (single dose) C min(desired )
T
C min(1) C max(1) e k e T ke

Peak (multiple dose) Calculated recommended dose

D


1 e k e T 1 e
k e
C max D C max( desired ) k e VT

CL T 1 e k e 1 e
k e T

Trough (multiple dose)

Two-Compartment-Body Model
C a e t b e t
C min C max e k e T
AUC a / b /
Calculated elimination rate constant
Vd area Vd ss Vc
C
ln max
C min Creatinine Clearance
ke
t
with Cmax = measured peak and Cmin* =
*
(140 age) weight
CL creat ( male)
measured trough, 72 Cp creat
measured over the time interval t
(140 age) weight
CL creat ( female)
85 Cp creat
With weight in kg, age in years, creatinine plasma conc.
in mg/dl and CLcreat in ml/min
Equations/Useful_pharmacokinetic_equ_5127 2
Ke for aminoglycosides
Ke = 0.00293(CrCL) + 0.014

Metabolic and Renal Clearance

Cl int fu b
EH =
QH Cl int fu b

QH Cl int fu b
ClH = EH QH =
QH Cl int fu b

QH
FH =
Q H Cl int fu b

C in C out
Clren = RBFE = GFR
C in

rate of excretion
Clren =
plasma concentration
Rate of secretion - Rate of reabsorption
Clren = fu GFR
Plasma concentration

Urine flow urine concentration

Clren =
Plasma concentration

Ideal Body Weight Volume of Distribution

V VP VT K P
Male fu
V V P VT
IBW = 50 kg + 2.3 kg for each inch over 5ft in fu T
height

Female Clearance
IBW = 45.5 kg + 2.3 kg for each inch over 5ft in
height Dose
Cl
AUC
Obese
ABW = IBW + 0.4*(TBW-IBW) Cl ke Vd

Equations/Useful_pharmacokinetic_equ_5127 3
For One Compartment Body Model

For a single I.V. bolus administration: For multiple I.V. bolus administration:

C0
D D 1 e nke
e ket
V Cn(t )

V 1 e ke
If the dosing
C C0 e k e t at peak: t = 0; at steady state n
involves the use at trough: t =
of I.V. bolus
D 1
administration: C max ss
V ( 1 e ke )

Cmin ss Cmax ss e k e

For a single short-term I.V. infusion: For multiple short-term I.V. infusion at steady state:

D 1 e k eT
Since = t for Cmax

If the dosing
involves the use
Cmax
D
VkeT

1 e k eT Cmax
VkeT 1 e k e
of I.V. infusion:

C e k e ( T )
Cmin Cmax e k e ( T )
C min max

Last modified 2010

C:\Current Data\pha5127_Dose_Opt_I\equations\5127-28-equations.doc
 Ct
D
VkeT

e k eT 1 e ket (most general eq.) during infusion t = T so,

If the dosing
involves a I.V.
Ct
D
VkeT

1 e k et (during infusion) at steady state t , e , t 0 so,
-ket

infusion (more
equations): D k k D
Cpss 0 0 (steady state) remembering k 0 and
VkeT Vke CL T
CL V ke

C F D ka
For a single oral dose: For multiple oral doses:
F D ka e ket ekat
C e ket e k a t
If the dosing
involves oral
V k a k e

V k a ke 1 e k e 1 ek

a

ka
1
administration:
1
t max ln k 1 e k e
k e k a k e t max ln a

ke 1 e k a ka ke

Last modified 2010

C:\Current Data\pha5127_Dose_Opt_I\equations\5127-28-equations.doc