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   kmaxt 
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 VT

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 = RBFE = 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 ekat
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  ek

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