Question 1. The data in Table 1 was collected during and after a two hour IV infusion at a rate of 150 mg/hr. Graph the data on semi-log graph paper and calculate initial estimates of kel and V.
| Time (hr) | Cp (mg/L) |
| 0 | 0 |
| 1 | 1.95 |
| 2 | 4.0 |
| 3 | 2.9 |
| 4 | 2.5 |
| 5 | 1.8 |
| 6 | 1.6 |
| 7 | 1.28 |
Question 2. Fit the data in Table 1 using the initial estimates determined in Question 1 using a non-linear regression program. Analysis the data twice. Use a weighting scheme proportional to 1/val2 and also use a scheme where the data points are given equal weight.
Question 3. A given drug follows linear one compartment pharmacokinetics. If the drug half-life is 17 hr and the apparent volume of distribution is 19 L, calculate the IV infusion necessary to achieve a steady state concentration of 15 mg/L (1). What IV bolus loading dose would you use to achieve 15 mg/L more rapidly (2)? What rapid IV infusion rate would you need to get to 15 mg/L in 30 minute (3)? Describe all three dosing regimen and sketch (not graph) the three plasma concentration versus time profiles.
Question 4. Given the model below with ke and km first order excretion and metabolism rate constants, respectively, and k0 representing a zero order infusion, write the differential equation for Xu and determine the integrated equation for Xu using the Laplace transform method. (Hint: You will need the d.e. and Laplace equation for Xp first, also you will need the Laplace table for the back transform...why?].
------ ------
k0 | | ke | |
----> | Xp | -----> | Xu |
| | | |
------ ------
\
\ km
\
\ |
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