Download PK - 11-19

PHARMACOKINETICS
PK & PD OF PROTEIN
THERAPEUTICS
PROTEIN THERAPEUTICS
 Which of the following types of antibodies can produce the
most serious ef fect in humans?
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A. Neutralizing antibodies
B. Non-neutralizing antibodies
C. Cross-reactive antibodies
D. Sustaining antibodies
PROTEIN THERAPEUTICS
 What are some key dif ferences between small molecule drugs
and biologics?
 Production process
 Administration
 Transport
 What are examples of methods of elimination of proteins?
 What are two ways that biologics can move across
vasculature?
 Biologic drugs often exhibit high or low volume of
distribution? Explain your answer.
CLEARANCE
PROTEIN THERAPEUTICS
 For target-mediated drug disposition, what happens to CL
when there’s an increased concentration of drug?
 A. Increases
 B. Decreases
 C. Nothing
 The more _________ the biologic, the ___________ the
immunogenicity.
 A. Humanized, more
 B. Non-human, less
 C. Humanized, less
PK/PD
PK/PD
 When do we need PD monitoring?
 What does EC50 measure? What about Emax?
 Drug A EC50= 14. Drug B EC50=200. Which is more potent?
PK/PD
 Which of the following are characteristics that may mean the
drug should be monitored using Pharmacodynamics instead of
Pharmacokinetics?
 A. The drug concentrations are predictive of the effect
 B. When pharmacokinetic variability is much bigger than
pharmacodynamic variability
 C. When pharmacodynamic variability is much bigger than
pharmacokinetic variability
 D. Both A and D
PK/PD
PK/PD
 Calculate the loading dose to produce and maintain 90% of
Emax. V=40 L, CL=2 L/h, EC50=4mg/L
 LD=Ec50X Vd=160 mg
 90/(100-90)*160 mg=1440 mg
PK/PD
Describe:
1. Phase 3
2. Phase 2
3. Phase 1
PK/PD
 Follow up question:
 How can the effect remain constant if the concentration is declining
rapidly?
PK/PD
 For a sigmoid Emax model, what happens when you increase n?
(Number 2 on recitation)
 A. Increase the Emax and increase the range of concentrations
associated with 20 to 80% maximal effect
 B. Have NO effect on Emax and decrease the range of concentrations
associated with 20 to 80% maximal effect
 C. Increase the Emax and decrease the range of concentrations
associated with 20 to 80% maximal effect
 D. Have NO effect on Emax and increase the range of concentrations
associated with 20 to 80% maximal effect
 E. None of the above
PK/PD
PK/PD
6.1: D50=Ec50XVd
D50=11*33=360 mg
6.2: DR50=EC50XCL
DR50=11X2.64=29
6.3: 58/(100-58)*360
200/(344-200)*360=500mg
MD= 58/(100-58)*29=40 mg/hr
Fc= Css, max/Css, min
Fe=Css,max/Css, min (EC50 + Css,min/(EC50
+ Css, max)
PK/PD
 In comparing the fluctuation of concentration (Fc) to the
fluctuation of ef fect (Fe), which is true?
 A. Fc is always less than Fe
 B. Fe is less than Fc
 C. Neither
PK/PD
 Hysteresis: which causes counterclockwise or clockwise or neither
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Indirect link?
Functional tolerance?
Metabolic tolerance?
Sensitization?
PK/PD
THINGS TO KNOW
 Understand each phase of the curve
 Be able to calculate: D/DR50, or any % for D/DR50, Fc, Fe,
Concentration
 Which things are counterclockwise/clockwise
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5. EC50=1 .8 mmol/L
Emax=114 mm Hg
N=3.79
What potassium level is necessary to maintain at least 80% of
maximum muscle strength?
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E=0.8*114=91.2=Emax X C^n/(Ec50^n + C^n)
91.2=114X C^3.79/(9.3 + C^3.79)
846 +91.2C^3.79=114C^3.79
846=C^3.79 (114-91.2)
846=C^3.79 (22.8)
37.2=C^3.79
QUESTIONS?