PHAR 4634 Fall 1995

Pharmaceutics III

OU HSC College of Pharmacy

Final Exam

14 December 1995

Section ONE. Sketch a Graph or Diagram - 8 x 3 = 24 points

Sketch the graphs or diagrams requested in the space provided. Make sure you carefully include any distinguishing characteristics. Assume that a linear one compartment model applies for each sketch unless otherwise specified. Don't forget to include labels and units for each axes of a graph.

Q 1.1 Sketch the components of the G.L.C. assay method. Label three components.

3" x 2.5" space for sketch

Q 1.2 Draw a diagram showing the components of a linear two compartment model after an IV bolus dose. Give the differential equation for the plasma compartment.

3" x 2.5" space for sketch

Q 1.3 Linear plot of Cp versus time after an IV infusion for 3 hours, show Cp versus time for 12 hours.

3" x 2.5" space for sketch

Q 1.4 A Scatchard plot representing 1:1 drug protein binding with one type of binding site.

3" x 2.5" space for sketch

Q 1.5 Sketch a simplified model of a biological membrane

3" x 2.5" space for sketch

Q 1.6 Sketch a linear graph of effective t50% versus log(Dose) for a drug which is eliminated by two pathways; one a linear pathway and the other saturable.

3" x 2.5" space for sketch

Q 1.7 Semi-log plot of Cp versus time after a 2 hour IV infusion for a drug which exhibits two-compartment pharmacokinetics. Show Cp for 12 hours.

3" x 2.5" space for sketch

Q 1.8 Sketch the components used in the beaker laboratory experiment representing multiple IV bolus dosing.

3" x 2.5" space for sketch

Section TWO. True/False - Check the Correct Response. 8 x 2 = 16 points

Q 2.1 The E.M.I.T. assay method uses an enzyme-substrate reaction as the means of quantitating drug concentrations. True False

Q 2.2 The types of detectors used with H.P.L.C. include FID, EC, and MS. True False

Q 2.3 Appropriate units for AUMC are amount.volume^-1.time². True False

Q 2.4 Elimination of salicylate, a weak acid, is faster when the urine pH is 7.5 compared with when the urine pH is 8.5. True False

Q 2.5 Phase II metabolism processes commonly result in metabolites which have smaller molecular weight than the parent drug. True False

Q 2.6 The parameter MAT has the units of time^-1. True False

Q 2.7 For a drug like phenytoin which exhibits Michaelis-Menten elimination kinetics, when Km is much lower than plasma concentrations elimination will appear to follow first order kinetics True False

Q 2.8 A drug will tend to be extensively removed by hemodialysis if it has good water solubility and is highly bound to plasma protein. True False

Section THREE Calculations 10 + 14 + 12 + 16 + 8 = 60 points

Show all your work for full credit. All material not deleted or crossed-out will be considered for grading.

Q 3.1 (10 points) A drug was given to a number of subjects by a single IV bolus dose (250 mg) and then as a single oral dose (400 mg), after a suitable wash-out period. The average data are presented below. Complete the tables and calculate MRT(IV), MRT(PO), MAT, and the absolute bioavailability of the oral dosage form.

Time (hr)

Concentration (mg/L)

AUC

AUC

Time (hr)

Cp*t

AUMC

AUMC

0

13.51

0.00

0.00

0

0.00

0.00

0.00

0.5

11.75

6.32

6.32

0.5

5.87

1.47

1.47

1

10.21

1

10.21

4.02

5.49

2

7.72

2

15.44

12.83

18.32

4

4.41

12.13

4

17.64

33.07

6

2.52

6.93

6

9

1.09

5.41

9

9.79

0.00

3.88

0.00

48.82

Time (hr)

Conc (mg/L)

AUC

AUC

Time (hr)

Cp*t

AUMC

AUMC

0

0.00

0.00

0.00

0

0.00

0.00

0.00

0.5

10.84

0.5

5.42

1.36

1.36

1

13.72

1

2

12.53

13.13

2

25.06

19.39

4

7.47

20.00

4

29.87

54.93

6

4.27

6

9

1.84

9.18

9

16.60

63.37

0.00

6.59

0.00

82.83

MRT(IV)

<-------->

<-------->

MRT(PO)

MAT

F

Q 3.2 (14 points) A 200 mg dose IV bolus dose was given to a subject. After 8 hours another IV bolus dose of 150 mg was administered. Twelve hours after the first IV bolus dose an IV infusion of 40 mg/hr was started. If the elimination rate constant is 0.12 hr^-1 and the apparent volume of distribution is 37 L, calculate the plasma concentration 2 hours after the IV infusion was started.

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Q 3.3 (12 points) A 40 year old man (80 kg) is to be started on phenytoin once a day. He was initially given 375 mg/day for two weeks. A plasma concentration was collected and measured at 12.9 mg/L. The dose was increased to 425 mg/day and another sample was collected after a further two weeks. This time the concentration was 20.4 mg/L. Calculate the Vm and Km value for this patient and a suitable daily dose to achieve a plasma concentration as close as possible to 15 mg/L. The only available capsule sizes are 25, 50, 100, and 250 mg. Calculate the expected plasma concentration.

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Q 3.4 (16 points) A drug was given by IV bolus (300 mg) and the following data were collected. Calculate A, B, , , k12, k21, kel, V1 and Varea. Label and give units for the graph axes.

Time (hr)

Concentration (mg/L)

<---------->

<---------->

<---------->

0

0.25

15.0

0.5

12.5

0.75

10.5

1

9.0

2

5.9

3

4.5

4

3.6

6

2.4

9

1.3

12

0.7

<------->

<------->

<------->

A

B

k21

k12

kel

V₁

V_area

Three cycle semi-log graph paper provided

Q 3.5 (8 points) Calculate an IV bolus loading dose and an IV maintenance infusion for a 45 year old (78 kg) male patient (height 6'0") to rapidly reach and maintain a plasma concentration of 20 mg/L. Assume a linear one compartment pharmacokinetic model with t_1/2 = 5.7 hr and V = 0.25 L/kg.

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