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Clinical - Pharmacokinetics
Clinical - Pharmacokinetics
CLINICAL
PHARMACOKINETICS
HOW TO USE THIS POWERPOINT
PRESENTATION
▪Review of Concepts
Clearance, K, Half-Life, Volume of Distribution
▪Therapeutic drug Monitoring
▪ Cases
▪ Discussion/Questions
PHARMACOKINETICS (PK) &
PHARMACODYNAMICS
(PD)
▪ PK - What the body does to the drug?
Absorption; distribution, metabolism, excretion (ADME)
Plasma Site
Concen- of
Dose Effects
tration Acti
on
PK PD
PHARMACOKINETICS VS
PHARMACODYNAMICS…CONCEPT
▪ Fluoxetine increases plasma concentrations of amitriptyline.
This is a pharmacokinetic drug interaction.
Volume 100 L
Clearance
10 L/hr
Volume of Distribution, Clearance and
Elimination Rate Constant
V
V2
Cardiac and
Skeletal Muscle
Clearance
10 L/hr
V2
Cardiac and
Skeletal Muscle
V
Volume 100 L (Vi)
Clearance
10 L/hr
Volume of Distribution =
Dose Plasma
Concentration
V2
Cardiac and
Skeletal Muscle
V
Volume 100 L (Vi)
Clearance
10 L/hr
Clearance =
Volume of blood cleared of drug per unit time
V2
Cardiac and
Skeletal Muscle
V
Volume 100 L (Vi)
Clearance
10 L/hr
Clearance = 10 L/hr
Volume of Distribution = 100 L
What is the Elimination Rate Constant (k) ?
CL = kV
k = 10 Lhr -1 = 0.1 hr -1
100 L
▪ An abstract concept
Dose = Cp(Target) x VD
QUESTION
Exponential decay
dC/dt C
= -k.C
C2
Tim
e
Log Concn.
C0
C0/2
t
1/2
t1/2
t1/2
T
i
Integrating:
Cp2 = Cp1.e-kt
Logarithmic transform:
lnC2= lnC1
- kt
logC2 = logC1 -
kt/2.303
Elimination Half-Life:
t1/2
t1/2 = 0.693/k
= ln2/k
STEADY-STATE
▪Steady-state occurs after a drug has been
given for approximately five elimination
half-lives.
▪At steady-state the rate of drug
administration equals the rate of
elimination and plasma
concentration -
time curves found after each dose should
be approximately superimposable.
Accumulation to Steady State
100 mg given every half-life
194 … 200
187.5
175
150
100
97 … 100
87.5 94
75
50
C
Cpav
MONITORPrIinNcip
Gles
THERAPEUTIC INDEX