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 Semilog plot of Cp versus time after a 2 hour IV infusion for a drug which exhibits twocompartment 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
Q 2.1 The E.M.I.T. assay method uses an enzymesubstrate 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}.time^{2}. 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 MichaelisMenten 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
Show all your work for full credit. All material not deleted or crossedout 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 washout 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 



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<> 
<> 
A 


B 








k21 


k12 


kel 


V_{1} 


V_{area} 


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.