Transcript 10-6-2016 PPT

PHARMACOKINETICS
PROTEIN BINDING
PROTEIN BINDING
 A certain drug is 80% protein bound. Another drug is given
that decreases the protein binding to 60%. Which of the
following would change?
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A. Loading dose
B. Maintenance dose
C. Half life
D. AUC, unbound
E. None of the above
PROTEIN BINDING
 Which of the following do NOT af fect the half life of a drug?
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A. fut
B. fup
C. CLu
D. Vt
 Which of the following MUST change for you to change the
LD?
 A. CLu
 B. fup
 C. fut
 Which of the following MUST change for you to change the
MD?*
 A. CLu
 B. fup
 C. fut
PROTEIN BINDING
 What type of drugs does albumin bind?
 A. Acidic
 B. Basic
 What type of drugs does AAG1 bind?
 A. Acidic
 B. Basic
 Which type of protein has high capacity, but low affinity?
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A. Transcortin
B. Albumin
C. Thyroid binding globulin
D. A and C
 Which type of protein has low capacity, but high affinity?
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A. Transcortin
B. Albumin
C. Thyroid binding globulin
D. A and C
PROTEIN BINDING
 A drug is 75% protein bound with a
therapeutic range of 10 to 20 mg/L.
Calculate the unbound, therapeutic
range of the drug.
 When are can you simplify this formula?
 A. When the drug is bound to a high
capacity, low affinity protein such as albumin
 B. When the drug is bound to a low capacity,
high affinity protein such as transcortin
 C. When 1/Ka>>Cu
 D. When 1/Ka<<Cu
 E. A and C
PROTEIN BINDING
 When you do simplify the formula,
what are you saying?
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A. fu is only affected by N and Ka
B. Cu affects fu
C. fu and Cu are independent
D. A and C
 If you have a protein that tends to
become saturated with a drug,
what does this mean?
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A. fu is only affected by N and Ka
B. Cu affects fu
C. fu and Cu are independent
D. A and C
PROTEIN BINDING
 For a drug that primarily binds
albumin, what happens to fup if you
increase Ka?
 A. Increase fu
 B. Decrease fu
 C. Nothing, they are independent
 For a drug that primarily binds
albumin, what happens to fup if you
decrease Cu?
 A. Increase fu
 B. Decrease fu
 C. Nothing, they are independent
PROTEIN BINDING
 Prednisone binds transcortin and albumin, while
methylprednisolone only binds to albumin. How does the fu
for each drug change with increasing plasma concentration?
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A. Fu, prednisone is the SAME, fu, methylpred INCREASES
B. fu, prednisone INCREASES, fu, methylpred is the SAME
C. fu, pred INCREASES, fu, methylpred DECREASES
D. fu, pred is the SAME, fu, methylpred is the SAME
 Based on the answer, what happens to:
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CL
CL,u
Vss
Vss,u
t1/2
PROTEIN BINDING
 A drug is able to displace two drugs: Drug A ( fup=0.001) and
Drug B (fup=0.5). Which drug interaction has the biggest
therapeutic impact?
 A. Drug A
 B. Drug B
 If fut >> fup, what does this mean?
 A. Volume of distribution is very low
 B. Volume of distribution is very high
 C. Neither, unable to tell from this information
PROTEIN BINDING
 What should you look at to determine the volume of
distribution?
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A. fup
B. fut
C. Neither
D. Ratio of fup and fut
PROTEIN BINDING
 In the aspirin phenytoin example, aspirin increased the fup of
phenytoin. Why was the LD not changed?
 In the aspirin phenytoin example, aspirin increase the fup of
phenytoin. Why was the MD not changed?
 If fu increases, what happens to Clu? CL?
 What is CLu a measure of?
PROTEIN BINDING
 A CKD receiving phenytoin ( Css=8mg/L in) has an albumin
level of 2g/dl. Determine how to manage the patient. Normal
levels are Css= 10-20mg/L, Css,u=1-2mg/L.
 A. Increase dose, since 8mg/L is below Css
 B. Decrease dose
 C. Leave dose the same
PROTEIN BINDING
 If Drug A is given with Drug B which causes a displacement of
A from tissue binding sites only, therefore doubling fraction
unbound in tissues. Determine what happens to the following
parameters:
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t1/2
AUC,u
AUC
Vss,u
Vss
CL,u
CL
PROTEIN BINDING
 When valoproic acid is given with phenytoin, phenytoin’s
plasma protein binding decreases from 90% to 84%. Also,
valproic acid decreases the unbound CL of phenytoin, and
displaces phenytoin from tissue binding sites; no change in
half-life.
 What happens to…
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AUC?
AUC,u?
LD?
MD?
HEPATIC CLERAANCE
HEPATIC CLEARANCE
 If a patient is on 600mg BID IV of Linezolid. The medical team
wants to switch the patient to oral therapy. What dose should
you recommend? Fe=1
HEPATIC CLEARANCE
 Calculate F* for a drug that has a ER of 0.3.
 Calculate F for a drug with the following characteristics:
fa=0.2, fg=0.1 , ER=0.3
 A drug with an F* of 0.1 is classified as high or low
extraction?
 Enzyme induction or inhibition occur almost immediately?
 For a drug with a ER=0.2, what is CL dependent on?
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A. Q
B. fu
C. CL,int
D. B and C
 For a drug with a ER=0.99, what is CL dependent on?
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A. Q
B. fu
C. CL,int
D. B and C