Download 11-2-2016 PPT

PHARMACOKINETICS
VOLUMES AND PROTEIN
BINDING
VOLUMES AND PROTEIN BINDING
 Which of the following alteration in protein binding is likely to
be the most clinically significant acutely?
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A. Volume of distribution=2, fut is increased
B. Volume of distribution=150, fut is decreased
C. Volume of distribution=2, fut is decreased
D. Volume of distribution=150, fup is increased
VOLUMES AND PROTEIN BINDING
 If fup is increased, which of the following situations would
most likely require a change in MD?
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A. Low E drug IV
B. Low E drug PO
C. High E drug IV
D. High E drug PO
VOLUMES AND PROTEIN BINDING
 When do you see a “spike” on the time vs concentration graph
(aka transient increase) when fup is increased?
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A. Both PO and IV Low E drugs
B. High E drug given IV
C. Only Low E drug given IV
D. High E drug given PO
E. Both A and D
VOLUMES AND PROTEIN BINDING
 When are you likely to see a clinically significant effect if fup is
changed?
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Low or High protein binding?
Wide or narrow therapeutic index?
High or Low E drug?
IV or PO?
VOLUMES AND PROTEIN BINDING
 Which of the following would result in the most clinically
significant (concerning) situation?
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A. Nonlinear elimination
B. Nonlinear plasma protein binding
C. Both
D. Neither
VOLUMES AND PROTEIN BINDING
 Describe the phases of nonlinear protein binding:
DOSE DEPENDENCE
DOSE DEPENDENCE
 CL,T=300 ml/min, fe=0.1. If this drug exhibits non -linear
pharmacokinetics, what will be af fected causing an increase
in AUC?
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A. Because
B. Because
C. Because
D. Because
it is a high extraction drug, the CL will be affected
it is a low extraction drug, the CL will be affected
it is a high extraction drug, the F will be affected
it is a low extraction drug, the F will be affected.
DOSE DEPENDENCE
High Extraction Drugs
 CL=
 F*=
 Non-linear PK
manifests in:
 Terminal slope will be:
 Half life:
Low Extraction Drugs
 CL=
 F*=
 Non-linear PK
manifests in:
 Terminal slope will be:
 Half-life:
DOSE DEPENDENCE
DOSE DEPENDENCE
DOSE DEPENDENCE
QUESTIONS?