PHAR 7632 Spring 1999
Biopharmaceutics
OU HSC College of Pharmacy
Final Exam 5 May 1999
Section ONE. Sketch a Graph or Diagram–Sketch the graphs or diagrams requested in the space provided. Include any distinguishing characteristics. Assume that a linear one compartment model applies unless otherwise specified. Include labels and units. 8 x 3 = 24 points
Q 1.1 Semi-log plot of cumulative amount of unchanged drug into urine versus time after a single IV bolus dose.
Q 1.2 Linear plot of rate of excretion into urine of unchanged drug versus time.
Q 1.3 Sketch the first few steps in the simplex optimization of a two parameter model on a WSS surface.
Q 1.4 Semi-log plot of amount remaining to be excreted as unchanged drug into urine versus time.
Q 1.5 Diagram illustrating a one compartment model after an IV bolus with excretion of unchanged drug and one metabolic pathway for elimination.
Q 1.6 A sketch illustrating Euler's method of numerical integration.
Q 1.7 A sketch illustrating the calculation of AUC between two data points.
Q 1.8 A fluorescence detector labeling three parts of the detector.
AnswersSection TWO. True/False–Check the Correct Response. 8 x 2 = 16 points
Q 2.1 Mathematical models are defined with the SAAM II program using FORTRAN, a computer language. True False
Q 2.2 The Nelder-Mead optimization method is a very fast method because it uses complex calculations to move quickly across the WSS surface. True False
Q 2.3 The finger print method for back transforming Laplace transforms requires the numerator have a higher power in 's' than the denominator. True False
Q 2.4 WinNONLIN can be used to calculate concentration versus time data using given parameter values or to find best values for parameters. True False
Q 2.5 Using the 1/Value2 method of weighting means that data points with smaller values are given more emphasis. True False
Q 2.6 Appropriate units for Rate of Excretion are mg.hr. True False
Q 2.7 The Marquardt method of optimization provides a mix between the Gauss Newton and the steepest descent method. True False
Q 2.8 Appropriate units for fe include mg/hr. True False
AnswersSection THREE Calculations This section = 15 + 25 + 10 + 10 = 60 points
Show all your work for full credit. All material not deleted or crossed-out will be considered for grading. Put labels and units on all graphs.
Q 3.1 (15 points) Derive the integrated equation for M2 in the following model after an IV bolus dose using the Laplace transform method.
Q 3.2 (25 points) A 400 mg dose of a drug was given by IV bolus and the data below was collected. Plot the appropriate data on semi-log graph paper, draw the ‘best’ line and determine ke, km, kel, fe, and fm from these data.
|
Time (hr) |
Urine Volume (ml) |
Concentration in Urine (µg/ml) |
|||
|
0 |
|||||
|
0-1 |
80 |
440 |
|||
|
1-2 |
90 |
370 |
|||
|
2-4 |
190 |
280 |
|||
|
4-6 |
170 |
260 |
|||
|
6-9 |
Data Lost! oh no! |
||||
|
9-12 |
300 |
120 |
|||
|
12-24 |
1120 |
60 |
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Q 3.3 (10 points) Given that you want to maintain plasma concentrations above 2.5 mg/L for 12 hours, what IV bolus dose would be needed if t1/2 = 3.8 hr and V = 68.6 L? Assume a one compartment linear pharmacokinetic model. What would the expected Cp0 value be if this dose were given.
AnswersQ 3.4 (10 points) A drug is known to follow one compartment pharmacokinetics. The elimination rate constant in patients with normal renal function is approximately 0.39 hr-1, the apparent volume of distribution is 35.7L, and the value of fe is 0.35. Assume that metabolism is unaffected by changes in renal function. Calculate the expected elimination half-life in patients with only 30% of normal renal function.
Answers