PHAR 7632 Spring 1999

Biopharmaceutics

OU HSC College of Pharmacy

Second Semester Exam 1 April 1999

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 requested graphs.

Q 4.1 (20 points) A 250 mg dose of a drug was given by IV bolus and the data below was collected. Plot the data on semi-log graph paper, draw the ‘best’ line and determine Cp0, kel, V and AUC (using the trapezoidal rule) from these data.

First plot the data

The best fit line should go between the first two and the last two data points.

Thus, Cp(0) = 3.16 mg/L and Cp(26.4) = 0.1 mg/L

kel = (ln 3.16 - ln 0.1)/26.4 = (1.15 - - 2.30)/26.4 = 3.45/26.4 = 0.131 hr^-1 (- don't just use points from the table, especially the first and second points (see graph)

V = Dose/Cp(0) = 250/3.16 = 79.1 L

Q 4.2 (10 points) Given that you want to maintain plasma concentrations above 5 mg/L for 8 hours, what IV bolus dose would be needed if t_1/2 = 5.2 hr and V = 17.9 L? Assume a one compartment linear pharmacokinetic model. What would the expected Cp⁰ value be if this dose were given.

kel = ln 2/t_1/2 = 0.693/5.2 = 0.133 hr^-1
Since Cp = (Dose/V) * exp(-kel*t)
Dose = Cp * V / exp(-kel*t)
    = 5 x 17.9 / exp(-0.133 x 8)
    = 89.5 / 0.345 = 259 = 260 mg

Cp⁰ = Dose/V = 260/17.9 = 14.5 mg/L

Q 4.3 (13 points) Use the finger print method to determine the back transform of the equation:

Three terms, all different, in the denominator. Higher power (3 vs 1) in denominator than numerator.

Three roots are 0, -kel, and ka.

Thus:

X = (k0 * k12 * Dose * e^0*t)/(kel*ka) +
    (k0 * (k12 - kel) * Dose * e^-kel*t)/(-kel*(ka-kel)) +
    (k0 * (k12 - ka) * Dose * e^-ka*t)/(-ka*(kel-ka))