Calculate half-life and clearance and volume of distribution

Reference no: EM13995160

1) An intravenous dose of morphine was administered to a patient. The dose was 10 mg. The following plasma concentrations were measured

Time (h)	C (ng/mL)	Cu (ng/mL)
0,5	46
2	28	21,3
4	19
6	12
8	6,5
10	5

After 2 hours, measured both the total plasma concentration and the free, unbound plasma concentration. Urine was collected for 24 hours after the dose administered and the amount of morphine in omrändrad in the urine was 0.7 mg. Show your calculations!

a) Calculate the half-life, clearance and volume of distribution

b) Calculate hepatic clearance (CLH)

c) Which / what assumptions you need to make in b) above so that your answer should be relevant? Motivate your answer!

2)Three drugs exhibit the following properties. Clearance and fu are calculated based on the plasma data.

Medicine	Total CL (ml/min)	Renal CL (ml/min)	fu(-)
Theophylline	45	5,0	0,45
Gentamicin	110	110	0,90
Cephalexin	300	300	0,85

a. What is the conclusions about the mechanisms of renal elimination, that is, which of the mechanisms of glomerular filtration, active secretion and tubular reabsorption dominates for each medicine? Suppose GFR = 125 ml / min. Show your calculations!

b. When overdosing can some/some of the medicine accelerate the excreation by giving duiretics. If so, specify what medication / medications above it is and motivate your answer.

3)The drug X is used for hypertension. It is available in tablet strengths 100 and 200 mg. Bioavailability is 85%, the volume of distribution is 50 liters and the half-life is 11 hours. Suitable plasma concentration at steady state is about 5 mg / L.

a) A patient has high blood pressure. How often do we give the drug X to the patient that he'll get the right plasma concentration at steady state? Also indicate what the tablet strength, the patient should take.

b) How long will it take before the patient reaches the steady state level? Motivate your answer!

4)Decide whether the following statements are correct or not. The pharmacokinetics of the drug follow a specifically partment model (enkompartment modell). The half life of the drug is 12 hours. Justify your answer by showing your calculations.

a. The elimination rate constant is 0.058 h

b. It takes 60 hours for the 87.5% of the intravenous dose to be eliminated from the body.

c. It takes twice the time to eliminate low of 37.5 mg of the drug after an intravenous dose of 50 mg as compared to the time it takes to eliminate 50 mg for a dose of 100 mg.

d. The percentage of the dose remaining 24 hours after administration of a intravenösdos is 0.25.

5) The plasma concentration of the drug, memantine was followed over time. By affecting urinary pH could influence the pharmacokinetics of the drug result is shown in the figure below. The pH-values correspond to pH in the urine in the two cases.

1812_Plasma concentration.png

a. memantine Is a weak acid or a weak base? Motivate your answer!

b. How can you affect the pH of the urine so that it is alkaline or acidic? Motivate your answer!

c. From the figure above, what can you say about memantins hepatic clearance? High or low? Motivate your answer!

6) Answer the following questions about the metabolite kinetics:

a. The terminal half-pipecarbamazepine and the terminal half-life of its metabolite areunge Pärequal. What process is rate limiting for metabolite elimination? Motivate your answer!

b. The principal route of elimination of salicylic acid in humans is via glycine conjugation in the liver. Salicylic acid is eliminated extremely slowly from the body, while glycinemetabolite can be eliminat every quickly from the plasma and are 100% in the urine. The fact is that the plasma concentration of glycinemetabolite is so low that it is barely detectable. Why is it reasonable to assume that it is possible to determine metabolism kinetiken for glycine conjugationofsalicylic acid by measuring glycinmetaboliten in urine? Motivate your answer!

c. Draw schematic plasma concentration curvesofsalicylic acid and glycinmetaboliten in the same chart. The Y-axis will be logarithmic. Justify your answer with explanatory text to your charts!

Reference no: EM13995160

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