Question 1: Select the correct statement(s). The plasma drug concentration versus time curve for a two-compartment model is (5 points)

      1                biexponential

      2                monoexponential

      3                based on second order pharmacokinetic processes

      4                based on first order pharmacokinetic processes

The correct statement(s) are (is):

Question 2: We have defined several volumes of distribution when talking about a 2-compartment model (5 points).

Select from the following statements  the correct statement(s)

The volume of distribution in a 2 compartment model:

1 relates the amount of drug in the body to the plasma concentration

2 is decreasing with time after drug administration, as the amount of the drug in the body is decreasing

3 is increasing with time after drug administration until it reaches a plateau

4  is changing because it takes time for the drug to enter and leave the peripheral compartment.

Question 3-6:

      The following applies to questions 3-6: A 60-kg patient is begun on a continuous intravenous infusion of theophylline at 40 mg/hr (based on theophylline, not aminophylline). Forty-eight hours after beginning of the infusion, the plasma concentration is 12 mg/L.

      Question 3: If we assume that this concentration is at steady state, what is the theophylline clearance.  Please perform calculations on paper, we will check.  (5 points)

Select the correct answer A: 3.3 L/hr B: 0.3 L/hr C: 33 L/hr D: 198 L/hr E: None of the above

Question 4: If the volume of distribution is estimated to be 30 L, what is the half-life? Please perform calculations on paper. (5 points)

Select the correct answer A: 1.7 hr B: 6.3 hr C: 13.3 hr D: 22.1 hr E: 45.3 hr

Question 5: What would the plasma concentration be 10 hr after beginning the infusion. Show calculations. (5 points)

A:           3.2 mg/L

B :          4.8  mg/L

C:           8.1 mg/L

D:           11.0 mg/L

E:           None of the above.

Question 6: If the infusion is continued for 3 days and then discontinued, what would the plasma concentration be 12 hours after the stop of the infusion. Show calculations(5 points)

A            1.2 mg/L

B:           3.2 mg/L

C:           7.6 mg/L

D:           8.1 mg/L

E:           None of the above

Question 7: If the infusion is continued for 3 days at 40 mg/hr and the steady state concentration is 12 mg/L what infusion rate would likely result in a steady state concentration of 18 mg/L. Please perform calculations. (5 points)

A:   15 mg/L

B:    30 mg/L

C:     50 mg/L

D:     70 mg/L

E:     None of the above.

The following pertains to Questions 8-9

A 60 kg patient is started on 80 mg of gentamycin. Every 6 hr given as 1-hr infusion.

Question 8:  If this patient is assumed to have an “average” volume of distribution (value of the population mean) of 0.25 L/kg and a normal half –life of 3 hr, what would be the peak plasma concentration at steady state (the true C_max value).  Please provide calculations. (5 points)

Select the correct answer A: 3.2 mg/L B: 8.9 mg/L C: 12.2 mg/L D: 15.4 mg/L E: None of the above

Question 9: Based on above volume of distribution and t_1/2 estimates, is the 6 hr dosing interval sufficient to achieve a fluctuation of not more than 6.  Please provide calculations. (5 points)

Questions 10 -13

The following questions 10-13 are related to the equation shown below. Explain the meaning of the blocked parts of the equation in the following questions 10-13.

Question 10: What information does  D/Vd provide (5 points)

A:      C_max after the first dose when given as iv infusion

B:      Trough concentration at steady state when given as infusion

C:     C_max after the first dose when given as iv bolus

D:     Degree of accumulation

E:      Allows the calculation of the trough concentration, without this part of the equation , one would obtain C_max.

Question 11: What does this part of the equation tells us (5 points)

A:      Gives us the degree steady state has been reached during a constant rate infusion

C:     C_max after the first dose when given as iv bolus

D:     Degree of accumulation during multiple iv bolus injections

E:      Allows the calculation of the trough concentration, without this part of the equation , one would obtain C_max.

Question 12: What does this part of the equation provide (5 points)

A:        C_max after the first dose when given as iv infusion

B:        Trough concentration at steady state when  drug is given as infusion

C:        C_max after the first dose when given as iv bolus

E:        Allows the calculation of the trough concentration after multiple iv bolus injections, without this part of the equation, one would obtain C_max.

Question 13

Select the correct statement(s) The oral bioavailability of a drug whose  hepatic clearance is much smaller than the  liver blood flow  (5 points)

      1                will be small

      2                 will depend on liver blood flow

      3                 will depend on plasma protein binding

      4                 will be close to 100%.

      5                 will be affected by the GFR

Select the correct statements:

A:          1,  2,  3

B:         4

C:          5

D:          3,  4

E           2,  4

Question 14-18:    Patient 1 received a drug as an iv bolus injection. Pharmacokinetic and physiological characteristics, such as dose, fraction of the drug unbound in plasma and tissue, intrinsic clearance, liver blood flow, and volume of plasma and volume of the tissue water in this patient are shown below.

TABLE 1: INPUT PARAMETERS

The next table shows the resulting pharmacokinetic parameters in Patient 1. Let's assume a second patient receives the same dose of this drug, given as an iv bolus injection. Both patients differ only in the plasma protein binding to this drug. As you can see from the INPUT parameters, 100% of the drug in plasma is free for Patient 1. Contrary to this, in Patient 2, 33% of the drug present in plasma is free.

Please circle in the free column of the Table 2 for each parameter whether the parameter (Peak concentration, Ke, V, Cl, t_1/2, E, F, AUC ) will be  the same (B), will be  larger (A), or will be smaller (C) than those estimates observed in Patient 1.

Table 2: OUTPUT PARAMETERS

Question 22

The following concentration time profiles were observed after multiple bolus injections of a drug. The two curves differ in one of the input parameters (Dose, CL or Vd). (5pts)

Identify the one input parameter that differs:

Question 23:

Which of the following factors significantly affect the renal clearance of an unionized drug that shows complete passive renal reabsorption from the "urine" back into the blood: (5 pts)

1. plasma protein binding

2. activity of cationic transporters in the tubuli

3. urine flow

4. pH of urine

5. liver blood flow

Question 24-28 Mark whether the following statments are true or false

24. Loading doses are maily given for drugs with short half-life

25. A high volume of distribution will result in a high clearance

26. If Drug A is excreted by glomerular filtration as well as by hepatic metabolism and Drug B is cleared only by hepatic clearance, then in a patient with total renal failur, total body clearance of Drug A and B will be affected.

27. The oral bioavailability of a drug is determined significantly by the extraction ratio E.

28. The distribution of highly lipohpilic small drug molecules is perfusion rate limited.