Useful Pharmacokinetic Equations

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

C 
ln 1 
CL  C 2  ln C1 − ln C 2 Time of maximum concentration (single
ke = = =
Vd ( t 2 − t1 ) ( t 2 − t1 ) dose)
k 
ln a 
Half-life  ke 
t max =
t1 / 2 =
0.693 ⋅ Vd ln(2 ) 0.693
= =
(k a − k e )
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 ⋅τ ) ( )
1 − e − k a ⋅τ 

Initial concentration
Time of maximum concentration (multiple
D
C0 = dose)
( )
Vd
 k a ⋅ 1 − e− k e ⋅τ 
ln 
Plasma concentration (single dose)
t max =
 e
k ⋅(1 − e )
− k a ⋅τ 

C = C 0 ⋅ e− k e ⋅ t (k a − k e )
Plasma concentration (multiple dose)
Average concentration (steady state)
C 0 ⋅ e− k e ⋅ t F⋅ D
C=
( )
1 − e− k e ⋅τ C=
CL ⋅τ

Peak (multiple dose) Clearance

C0 Dose
C max = Cl =
( )
1 − e− k e ⋅τ AUC

Cl = ke ⋅ Vd
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Constant rate infusion
Calculated peak
Plasma concentration (during infusion) C∗
C max = − kmax⋅t ∗
k
(
C = 0 ⋅ 1 − e− k e ⋅ t
CL
) e e
with Cmax* = measured peak, measured at time
t* after the end of the infusion
Plasma concentration (steady state)
k Calculated trough
C= 0 ∗

CL C min = C ∗min ⋅ e − k e ⋅t

Calculated clearance (Chiou equation) with Cmin* = measured trough, measured at

2 ⋅ k0 2 ⋅ Vd ⋅ ( C1 − C 2 ) time t* before the start of the next infusion
CL = +
( C 1 + C 2 ) ( C 1 + C 2 ) ⋅ ( t 2 − t1 )
Calculated volume of distribution

Short-term infusion Vd =
D
⋅
1− e ( − k e ⋅T
)
k e ⋅ T C max − C min ⋅ e − k e ⋅T
Peak (single dose)
( )
D Calculated recommended dosing interval
C max(1) = ⋅ 1 − e − k e ⋅T
CL ⋅ T
 C max(desired ) 
Trough (single dose) ln 
 C min( desired ) 
C min(1) = C max(1) ⋅ e− k e⋅(τ −T ) τ= +T
ke

Peak (multiple dose)

Calculated recommended dose

C max =
D
⋅
(
1 − e− k e ⋅T ) (1 − e ) − k e ⋅τ

(
CL ⋅ T 1 − e− k e ⋅τ ) D = C max(desired ) ⋅ k e ⋅V⋅T⋅
(1 − e ) − k e ⋅T

Trough (multiple dose) Two-Compartment-Body Model

C min = C max ⋅ e − k e ⋅(τ −T) C = a • e − α t + b • e − βt

Calculated elimination rate constant AUC ∞ = a / α + b / β

 C∗  Vd area > Vd ss > Vc

ln max 
 C ∗min 
ke = Creatinine Clearance
∆t
with Cmax = measured peak and Cmin* =
*
(140 − age) • weight
measured trough, CL creat ( male) =
measured over the time interval ∆t 72 • Cp creat

(140 − age) • weight

CL creat ( female) =
85 • Cp creat

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With weight in kg, age in years, creatinine plasma conc. in mg/dl and CLcreat in ml/min
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

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