Problem Set on Pharmacodynamics and Pharmacokinetics

Due Tuesday, February 11th

Name ______________________

Instructions: Please complete this problem without the help of your classmates. Please see me during
office hours or by appointment if you would like any help.

Part 1: Pharmacodynamics. Below are some real data I collected doing a glutamate uptake experiment.
I plated astrocytes in a dish and applied mixtures of radioactive and nonradioactive glutamate. Because
I was measuring glutamate transport (and not binding of glutamate to a receptor), I measured velocity
instead of binding: pmoles of glutamate transported per minute, normalized to the amount of protein
(mg) in the cells. Use the figure to answer the following questions:

300
Glutamate Uptake Pharmacodynamics
Velocity/Concentration (pmol/mg/min/uM)

250

200

150
Control Condition
Experimental Condition
100

50
y = -0.0158x + 119.79 y = -0.0169x + 271.33

0
0 5000 10000 15000 20000
Velocity (pmol/mg/min)

1. What type of plot is this? (3 pts) ____________________________________________________

2. How many types of binding sites for glutamate do the transporters contain? (2 pts)____________
3. From visual inspection alone (before doing any calculations) which has changed? (5 pts)

a. Kd c. both
b. Bmax d. neither

4. For the both the control and experimental conditions, calculate Kd and Bmax. Please show your work
and make sure to include units. (20 pts)

5. Draw a rough sketch of the control and experimental data using a normal plot: i.e. % of total bound
ligand vs. concentration. Indicate Kd and Bmax on this sketch. You dont need to use exact numbers, but
the relative proportions should be close (10 pts)
6. Now draw a rough sketch of what the control data might look like if in addition to the specific
binding, there was also a considerable amount of nonspecific binding (again using a normal plot) (5 pts).

7. Name something that could be happening to glutamate transporters that could have this effect on
glutamate transport. (5 pts). (Bonus: 1 extra point if you can also guess what the experimental
condition is).

8. Which drug is more potent, A or B? (5 pts)

Part 2: Pharmacokinetics

9. Will a weak base with a pKa of 8.4 be best absorbed in the stomach or the intestine? Why? (5 pts)

10. After oral administration of 10mg of a drug, 50% is absorbed and 40% of the amount absorbed is
metabolized by the first pass effect. What is the bioavailable dose of this drug? Please show your work
and provide units for your answer. (5 pts)

11. A 10 mg/Kg dose of a drug is given by intravenous injection to a 20 Kg dog. What is the volume of
distribution of the drug if the plasma concentration is 0.1 mg/L (assume the drug is instantaneously
distributed)? What would the volume of distribution be if the same drug had been given orally and only
50% of the drug was absorbed (the concentration of drug at time = 0 is 0.1 mg/L)? Be sure to show your
work and provide units. (10 pts)
12. How much of a drug is eliminated after 4 half-lives? What will happen to elimination of the drug if
the system is saturated? (10 pts)

13. You have started a patient on a new drug. Each dose introduces 0.04 ng/mL of drug after
redistribution and prior to elimination. This drug is administered at 24 h intervals and has a half life of
24 h. What will the concentration of drug be after each of the first six doses? (10 pts)

Dose #1

Dose #2

Dose #3

Dose #4

Dose #5

Dose #6

14. If you wanted to reduce the difference between peak and trough levels that occur with repeated
administration of a drug, how would you adjust the dose and dose interval? Note: You dont want to
increase the plateau concentration (plateau is the average of peak and trough levels). Circle your
answers. (5 pts)

Dose Increase dose

Decrease dose

Do not change dose

Interval Increase the interval between doses (give the drug less frequently)

Decrease the interval between doses (give the drug more frequently)

Do not change the interval