Clinical Applications of

Pharmacokinetic Dosing and

Monitoring
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text)
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text)
• Exponential functions use ln, not log
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
• Doses and intervals normally change in quantum leaps!
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
• Doses and intervals normally change in quantum leaps!
• Unless otherwise indicated, assume bioavailability = 100%
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
• Doses and intervals normally change in quantum leaps!
• Unless otherwise indicated, assume bioavailability = 100%
• Unless indicated, assume instant absorption & distribution
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
• Doses and intervals normally change in quantum leaps!
• Unless otherwise indicated, assume bioavailability = 100%
• Unless indicated, assume instant absorption & distribution
• Focus mainly on math relationships, not manipulation of
equations
Assumptions and Ground Rules
for this Course
• Abbreviations and symbols from Rowland & Tozer (TMU Text
• Exponential functions use ln, not log
• Perspectives are from the patient care setting, not laboratory
• Doses and intervals normally change in quantum leaps!
• Unless otherwise indicated, assume bioavailability = 100%
• Unless indicated, assume instant absorption & distribution
• Focus mainly on math relationships, not manipulation of
equations
• Primary frame of reference for drugs in body will be BLOOD
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
• Drug is absorbed into serum/plasma
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
• Drug is absorbed into serum/plasma
• Drug distributes from serum/plasma
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
• Drug is absorbed into serum/plasma
• Drug distributes from serum/plasma
• Drug is eliminated from serum/plasma
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
• Drug is absorbed into serum/plasma
• Drug distributes from serum/plasma
• Drug is eliminated from serum/plasma
• Drug efficacy/toxicity relates to C in serum/plasma
Pharmacokinetic Frame of
Reference
Clinical Pharmacokinetics focuses on serum concentrations!
• Drug is absorbed into serum/plasma
• Drug distributes from serum/plasma
• Drug is eliminated from serum/plasma
• Drug efficacy/toxicity relates to C in serum/plasma
• Even though the drug probably acts elsewhere,
SERUM/PLASMA is the primary frame of reference for
pharmacokinetic monitoring
 SESSION 1
The Fish Tank - A Simplified
Model of First - Order Elimination
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
• Define V, CL, k and t½ and identify their practical applications
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
• Define V, CL, k and t½ and identify their practical applications
• Describe the applications of e-kt
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
• Define V, CL, k and t½ and identify their practical applications
• Describe the applications of e-kt
• Define AUC and describe factors that affect it; define MRT
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
• Define V, CL, k and t½ and identify their practical applications
• Describe the applications of e-kt
• Define AUC and describe factors that affect it; define MRT
• Identify how protein binding affects drug action, drug
distribution, and drug elimination
How can we describe what
happens to drugs in the body?
• Explain how fish tank relates to drug elimination
• Define V, CL, k and t½ and identify their practical applications
• Describe the applications of e-kt
• Define AUC and describe factors that affect it; define MRT
• Identify how protein binding affects drug action, drug
distribution, and drug elimination
• Explain how protein binding affects clearance
First-Order Elimination

Elimination
Rate of

Serum Concentration
The Fish Tank Model Applied to
Cl, V, k, and fu
Original Fish
Tank
circa 1979

Brown DL. The Fish Tank Model of First-Order Elimination: An Effective

Pharmacokinetic Teaching Tool. Currents in Pharmacy Teaching and Learning. 2013;
The Fish Tank:
V, C, CL, Rate of Elimination
The Fish Tank:
V, C, CL, Rate of Elimination
The Fish Tank:
V, C, CL, Rate of Elimination
The Fish Tank:
V, C, CL, Rate of Elimination
..... ..... ..... ..... .....
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..... ..... ..... ..... .....

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..... ..... ..... ..... .....

• Volume of Tank = 20 L
• Fish Added to Tank =
200
• Concentration = 10
Fish/L
The Fish Tank:
V, C, CL, Rate of Elimination
..... ..... ..... ..... .....
..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

• Volume of Tank = 20 L Time Fish Fish C Fish Lost/hr

• Fish Added to Tank = 0 200 10/L ---
200
• Concentration = 10
Fish/L
The Fish Tank:
V, C, CL, Rate of Elimination
..... ..... ..... ..... .....
..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

• Volume of Tank = 20 L Time Fish Fish C Fish Lost/hr

• Fish Added to Tank = 0 200 10/L ---
200 1 hr 156 7.8/L 44
• Concentration = 10
Fish/L
The Fish Tank:
V, C, CL, Rate of Elimination
..... ..... ..... ..... .....
..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

• Volume of Tank = 20 L Time Fish Fish C Fish Lost/hr

• Fish Added to Tank = 0 200 10/L ---
200 1 hr 156 7.8/L 44
• Concentration = 10 2 hr 121 6.0/L 35
Fish/L
The Fish Tank:
V, C, CL, Rate of Elimination
..... ..... ..... ..... .....
..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

..... ..... ..... ..... .....

• Volume of Tank = 20 L Time Fish Fish C Fish Lost/hr

• Fish Added to Tank = 0 200 10/L ---
200 1 hr 156 7.8/L 44
• Concentration = 10 2 hr 121 6.0/L 35
Fish/L 3 hr 94 4.7/L 27