Q1. The table below shows the plasma concentration data obtained after intravenous injection of a medicine. The dose is 100 mg. Calculate:
|
tid (h)
|
Cp (mg/L)
|
|
0, 1
|
13, 0
|
|
0, 2
|
11, 0
|
|
0, 3
|
10, 7
|
|
0, 4
|
9, 3
|
|
0, 5
|
9, 1
|
|
1
|
7, 2
|
|
2
|
6, 9
|
|
4
|
5, 3
|
|
6
|
5, 5
|
|
12
|
4, 0
|
|
18
|
3, 1
|
|
24
|
2, 0
|
|
36
|
1, 5
|
|
48
|
0, 5
|
a. The plasma half-life and elimination rate constant
b. The AUC and clearance
c. The volume of distribution
Q2. Renal clearance and hepatic clearance are important concepts in pharmacokinetics. At drug treatment is often appreciated renal function.
a. Describe in words how the estimated kidney function (eGFR) can be determined.
b. For some patients do a thorough experimental determination of renal function. How do you DETERMINE this?
c. The figure below shows a drug total body clearance as a function of EGFR. Assess the need to make a dose adjustment in patients with low eGFR values if the drug has a wide therapeutic window. Motivate your answer.
Q3. During the development of an oral preparation of a medicament studied plasma concentration over time after a 500-mg dose. The plasma concentrations were followed over 72 hours. The following data were obtained:
|
tid (h)
|
Cp peroral (mg/L)
|
|
0, 1
|
0, 0
|
|
0, 2
|
1, 4
|
|
0, 3
|
2, 6
|
|
0, 4
|
3, 8
|
|
0, 5
|
4, 8
|
|
1
|
5, 8
|
|
2
|
9, 4
|
|
4
|
12, 9
|
|
6
|
13, 6
|
|
12
|
12, 1
|
|
18
|
7, 6
|
|
24
|
4, 7
|
|
36
|
2, 9
|
|
48
|
1, 1
|
|
60
|
0, 4
|
|
72
|
0, 2
|
a. Calculate AUC
b. Is it possible to calculate the elimination rate constant, CL and Vd? Do it if it is based on the data you received in the task. If it cannot, the facts and data you need to calculate the elimination rate constant, CL and CEO. Motivate your answer!
Q4. When new drugs are developed, they require regulatory authorities (eg Medicines Agency and the FDA) that there is data on possible interactions with other drugs.
In this prospective case study of a drug that is metabolized by a single enzyme system to 100% in the liver to a single metabolite
a. Describe schematically by drawing a diagram of how the pharmacokinetics of drug change if it is administered orally alone or along with a strong inhibitor of the enzyme that metabolizes the drug.
b. Describe schematically by drawing a diagram of how the pharmacokinetics of metabolite change if the drug is administered alone, respectively along with a strong inhibitor of the enzyme that metabolizes the drug. Motivate your answer!
Q5. Since many drug metabolites are pharmacologically active, it is important to study metabolites kinetics.
Propranolol is metabolized to a metabolite whose kinetics was studied after intravenous administration (Panel A) and after oral administration (Chart B).
a. From the charts below which the rate constants determined the rate of elimination of the metabolite, the rate constant for the formation (KFM), or the rate constant of elimination (chem) of the metabolite?
b. Why the difference in metabolite AUC and AUC of propranolol as much higher after oral administration as compared to the difference in AUC intravenous administration?
Q6. In hall 8 is a 32-year-old recently given birth woman with newly diagnosed malignant tumor in the lower back. She will during the day to undergo a decompressive laminectomy (removal of the rear part of the arch rises to provide space for the spinal cord). She has severe pain which responded very poorly to codeine, although small doses of morphine intravenously administered when necessary has given good pain relief. During the round, she asks if she will be able to breastfeed her child despite all medications during and after surgery?
a. What could be a possible cause for the patient's response to morphine but not codeine?
b. What factors affect how a drug passes into breast milk?
c. If now the mother does not have any effect of koedein, there is no risk of child impact of codeine and may even suffer overdose effects?