1. Assuming a two compartment linear pharmacokinetic model, with kel = 0.14 hr-1, k12 = 1.2 hr-1, k21 = 1.5 hr-1; and V = 15.2 L, calculate the plasma concentration at 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after 250 mg i.v. bolus dose. Plot the data on linear and semi-log graph paper.
2. The data shown below were collected after an iv bolus of 300 mg. Using the method of residuals calculate A, B, alpha, and beta. Then calculate kel, k12, k21, Vc, and Varea.
Data Obtained after a 300 mg I.V. Bolus
|
Time (hr) |
Concentration (mg/L) |
|
0.125 |
14.0 |
|
0.25 |
11.5 |
|
0.5 |
8.42 |
|
0.75 |
6.81 |
|
1.0 |
5.95 |
|
1.5 |
5.19 |
|
2.0 |
4.88 |
|
3.0 |
4.53 |
|
4.0 |
4.23 |
|
6.0 |
3.71 |
|
9.0 |
3.05 |
|
12.0 |
2.50 |
|
18.0 |
1.68 |
|
24.0 |
1.13 |
3. Given that beta = 0.12 hr-1 and Varea = 19.2 L calculate an oral dosing regimen to achieve an average plasma concentration of 15 mg/L (Assume F = 0.85). HINT: You need to select a suitable value for tau (maybe one or two elimination half-lives)
Answer4. Given that Km = 5 mg/L and Vm = 8 mg/kg/day calculate the required daily dose rate to achieve an average plasma concentration of 24 mg/L in a 65 kg patient.
Answer5. A 72 kg patient was given 6 mg/kg/day for some time and the average plasma concentration was measured as 10 mg/L. Since this was too low the dose was raised to 8 mg/kg/day. Unfortunately this resulted in an average plasma concentration of 20 mg/L. Calculate Vm and Km and then calculate a dose rate which should achieve an average plasma concentration of 15 mg/L.
Answer6. A drug was administered both I.V. (150 mg) and P.O. (300 mg) to a subject. The AUC and AUMC from the iv data were 73.91 mg.hr.L-1 and 519.34 mg.hr2.L-1, respectively. The AUC and AUMC from the po data were 116.74 mg.hr.L-1 and 937.89 mg.hr2.L-1, respectively. Using non compartmental methods calculate all appropriate pharmacokinetic parameters.
Answer