1. The immunosuppressive drugs tacrolimushas the following pharmacokinetic parameters.

Cell Plasma = 4.2 L / hr

fu = 0.01

The blood to plasma ratio (Cb / Cp) = 33

a. “In principle, all the drug is eliminated via CYP3A4, plays only a negligible share of the systemic available dose is excreted unchanged in the urine.” Why are the above prerequisites necessary to be able to perform a correct calculation in the information below?

b. Is tacrolimus a high or lowextractiondrug? Assume that hepatic blood flow is 1500 ml / min.

c. If there is an induction of the enzyme CYP3A4, which changes in clearance and half-life you expect to tacrolimus? Justify response.

2. The table below shows the plasma concentration data obtained after intravenous injection of the study drug. The dose is 5 mg. You get asked to determine the new pharmacokinetic properties.

time (hours)	C (?g/L)	time (hours)	C (?g/L)
0,1	166	1,5	86
0,2	143	3	74
0,3	127	4	67
0,4	116	5	61
0,5	109	6	55
0,6	103	7	50
0,7	99	8	45
0,8	96	9	41
0,9	94	10	37
1	92	48	1

1. Calculate the plasma half-life and elimination rate constant

2. Calculate AUC and clearance

3. Calculate the volume of distribution

4. During the project meeting asking the manager (who is not an expert in pharmacokinetics) you to describe in words, study the drug’s pharmacokinetics. What do you answer?

3. Amoxicillin 500 mg was given as an intravenous injection to a patient. The following plasma and urine data were obtained. Plasma protein binding is 17%..

time (h)	Plasmakoncentration (mg/L)	amount (mg)
1	18	–
2	9	270
3	4,5	–
4	–	64
5	1,1	–
6	–	16
8	–	4

a. Calculate the half-life (t ½).

b. Calculate the CLV and fraction excreted unchanged in the urine (fe).

c. Renal CL and hepatic CL (assuming that elimination occurs only in the liver and through the kidneys).

d. Based on the pharmacokinetic properties of amoxicillin, amoxicillin may be effective against urinary tract infections? Give detailed reasons for your answer!

4. During the development of an oral formulation of a drug the studied plasma concentration over time after a 25 mg dose.

Previously known that t1/2 after an IV dose of the same medicine is 11.6 hours. The plasma concentrations were followed over 60 hours. The following data were obtained:

Time (hours)	C (?g/L)	Time (hours)	C (?g/L)
0,25	15	7	94
0,5	29	8	90
0,75	40	9	86
1	50	10	81
1,5	66	12	73
2	78	18	51
3	92	24	36
4	98	36	17
5	98	48	8,5
6	97	60	4

a. Determined the terminal portion of the plasma concentration curve of absorption and elimination? Draw a diagram and show your calculations!

b. How would the plasma concentration curve change if the absorption rate was halved? Plot the curve in the schematic diagram

c. How would the plasma concentration curve change if the absorption was 5 times faster? Plot the curve in the schematic diagram

5. A patient should begin treatment with a drug. Therapeutic range is 2.9 to 12 mg / L. Available doses ampoules 100, 200 and 400 mg for intravenous administration. Patient volume of distribution is 30 L and the clearance was 2.7 L / h.

a. What maintenance dose needed to maintain the concentration within the therapeutic range? Enter both dose and dosing interval.

b. How does the AUC of a single dose of AUC within a dosing interval at steady state upon multiple dosing? Motivate your answer!

6. Consider the figure below, which shows the plasma concentration of digoxin in the same figure as digoxinets effect. The arrows in the diagram shows the diagrams relating to the scale of the y-axes.

a. What is called this phenomenon – that is, the plasma concentration and effect of the drug does not coincide in time?

b. Provide a possible pharmacokinetic explanation for this phenomenon that occurs!

c. Give a possible pharmacodynamic explanation for this phenomenon that occurs!

7. The question is individual variation.

a. Describe the difference between a pharmacokinetic and pharmacodynamic variation.

b. Give two examples of factors that can give rise to inter-individual differences in pharmacokinetics.

c. A drug is largely metabolised by CYP2D6 is a polymorphic enzyme. What consequences can it have in regards to the dosage of the drug?