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Transcript
Introduction to Drug Disposition,
Clearance, Volume of Distribution,
and Intravascular Dosing
ALLIE PUNKE
PHARMACOKINETICS TUTORING
FALL 2016
This is only to be used as a guide
 I am not involved in the selection of test questions.
 This is not to replace studying for the exam; only to
supplement study.
 Just because it is discussed today does NOT mean it
will be on the test.
 Just because it is omitted in this review does NOT
mean it will be omitted from the exam.
Tips for Pharmacokinetics
 Learn the formulas!
 Know to go back and forth between each of them
depending on the type of information you were
given.
 Study especially hard for the first few exams…since
the material will build on itself
 Make sure to always look at the units
Introduction to Drug Disposition
 Pharmacokinetics:
 Pharmacodynamics:
 Pharmacogenetics:
 Pharmacogenomics:
 Pharmacometrics:
ADME
 Absorption:
 What are the two types?
 Distribution:
 Acidic drugs bind to ___________, while basic drugs bind to
_________________
 True or False: A drug that has a high Volume of distribution
(Vd) means that it is very hydrophilic.
ADME
 Metabolism:
 Which of the following is an example of a Phase II reaction?
A. Hydrolysis
 B. Methylation
 C. Reduction
 D. Oxidation
 E. A and B



What is the overall goal of liver metabolism?
Intestinal metabolism affects _________, while liver
metabolism affects ______________.
 Elimination:
 Liver or kidney
Rate of Kinetics
 True or False: Zero-Order kinetics removes a
constant fraction of drug
Zero Order
Dependent on
concentration?
Constant amount
or fraction
removed?
First Order
Rate of Kinetics
 Is this data an example of zero or first order?
Time (h)
Concentration
0
215
2
182
4
149
6
116
8
83
10
50
Rate of Kinetics
 What would the graph of the previous table look
like?
Clearance
 Clearance: The theoretical volume of blood from which
drug is irreversibly removed per unit time
 Equations for Clearance:


CL=
CL=
 A patient is given 500 mg of a new drug. Plasma
concentration entering the liver was 360 mg/L, and the
concentration exiting the liver was 95 mg/L. (Assume
liver blood flow is 81 L/h).



What is the ER of the drug?
Is it a high or low extraction drug?
What is the CL of the drug?
Clearance
 A patient is given 750 mg of a new drug. Plasma
concentration entering the liver was 165 ng/L. The
extraction ratio is 35%.

What is the concentration leaving the liver?
Clearance
 A patient is given 300 mg of a drug that has Vd of 75
L. Hepatic CL=900 ml/h, which is 60% of total CL.



What is the total CL?
How much is renal CL, if it is 10% of hepatic clearance?
What is the half-life of the drug?
Basics of CL and Vd
 True or False: If CL is increased, then Vd is also
increased.
 How many half lives does it take to reach steady
state?
 Calculating time to steady state:

If k=0.0144 h-1, then ____ hours to reach steady state
 Css occurs when _________ is equal to ________
 Css equation=
Intravascular Dosing
 What is the initial concentration if 1000 mg of drug
(Vd=0.7 L/kg) is given to a patient (90 kg) via IV
bolus?
 When would you expect to see the maximum/peak
concentration?
Intravascular Dosing
Time (hr)
Concentration
2
1.07 mcg/mL
10
0.342 mcg/mL
 Calculate the elimination
rate constant and the halflife of the drug.
Intravascular Dosing
 A drug is given to a patient and at hour 2 and 9, the
concentrations are 70 mg/L and 40 mg/L.

What is the half-life?

What is the initial concentration and concentration at hour 7.5.

How long will it take (starting from the time the drug was
given) for the drug concentration to reach 2.5 mg/L?
Intravascular Dosing
 What is the Vd (assume the dose was 2 grams)?
 What is the CL?
 What is the AUC?
Intravascular Dosing
 After an IV Bolus of 100mg of a drug, what is the
area under the curve? What are the correct units for
AUC?
Given k = 0.186 h-1 and Co = 6.0 mg/L
Questions?
[email protected]
ENJOY YOUR WEEKEND!