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Study Aids
• Anki Flash cards– Content that you need to know for the tests.
• MS Excel sheet with Calculations
PHARMACOKINETIC BASICSLecture #2
Factors in Measuring Systemic Exposure
• Sites of Measurement (Where?)• Unbound [Drug]• Exposure-Time Profile• Observation Period
Exposure-Time Profile
In addition to the concentration, what other factor should we consider with exposure?
Sites of Measurement
• Invasive– Whole Blood, Plasma and Serum• Unbound Drug Concentration and Fraction Unbound
• Non-invasive– Breath– Milk– Saliva– Feces– Urine
Chemical Purity/Enantiomers
anticoagulant
stimulant
Decreases Rapidly
[drug] very low
Active Metabolites and Prodrugs
Sites of Administration• Intravascular Systemic Circulation
– Intravenous (IV)– Intra-arterially (IA)
• Extravascular Absorption Systemic Circulation– Buccal (Between Cheek and Gum)– Intradermal (ID)– Intramuscular (IM)– Oral – Pulmonary (Inhalation)– Subcutaneous (Subcut, Fat under Skin)– Rectal– Sublingual (SL, under the tongue)
Typical Exposure-Time Profiles
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
Intravascular Extravascular
Lag due to absorption
[Dru
g]pl
asm
a
Parenteral Administration
• Restricted to Injected– Intravascular– Intramuscular– Subcutaneous
How a drug ends up- Drug Disposition
(i.e. Amount Absorbed)
ExcretedMetabolite
Terms
• Elimination– Drug Metabolism– Amount/time (mg/hr)
• Excretion– Drug Removal from the Body– Amount/time (mg/hr)
• Clearance– Volume/time (L/hr)
D[Drug] = [Drug]in –[Drug]out
DDrugDrug In
Drug Out
Representing PK
• Equations• Physiologic Models• Compartment Models
Equations
Why?
Physiologic Models
Compartmental Models
ADME
Systematic Absorption
First Pass Loss
Systemic Circulation
Bioavailability (F)
Enterohepatic Cycle: Drugs Recycled
PK Terms
• Maximum Concentration (Cmax)
• Maximum Time (tmax)• Area Under the Curve (AUC)
Cmax and tmax
Cmax
tmax
What factors determine how much exposure that you have to a “poison”?
• systemic exposure = How long * How much[D
rug]
plas
ma
time
Systemic Exposure
How longHow
much
What factors determine how much exposure that you have to a drug?
• AUC = How long * How much[D
rug]
plas
ma
time
Area Under the Curve (AUC)
How longHow
much
Area Under the Curve (AUC)
tmax
AUC(µg/L)*hr
Area Under the Curve
Drug Plasma After Intravenous (IV) Bolus Dose
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
C(0)
k=rate (/hr)
Drug Plasma After Intravenous (IV) Bolus Dose
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
C(0)
AUC
Cmax and tmax?
Trapezoid Area
a b
c
Trapezoid AreaCi
tfti
Cf
time
[Dru
g]
Drug Plasma After Intravenous (IV) Bolus Dose
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
C(0)
Drug Plasma After Intravenous (IV) Bolus Dose
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
C(0)
Ct
Drug Plasma After Intravenous (IV) Bolus Dose Only
0 2 4 6 8 10 120
2
4
6
8
10
12
time (hr)
[Dru
g]pl
asm
a
C(0)
Only works when the curve is shaped like this.