MAS286统计汇总

University of Sheffield

School of Mathematics and Statistics

MAS286 Mathematics and Statistics in Action

Spring Semester 2022/23

Please read the following instructions carefully before starting the assignment:

• Your assignment should be uploaded as a single PDF file to Blackboard by the deadline

of 10am on Monday 20th March. Please include your registration number in the

filename, with the convention 123456789_mas286_topic2.

• Any word processing software may be used, though LATEX is preferred. A sample LATEX

file can be found on Blackboard by clicking on ‘Assessment information’, then ‘Topic 2:

Pharmaco-kinetics (weeks 4-6)’ .

• The bulk of the marks will be for the mathematical work, but marks will also be awarded

for clear explanations.

• You may refer to and use all the numbered equations used in the lecture notes without

re-deriving them from scratch.

• For some questions you will need to derive the formulae for the dynamics from the

differential equations given, and for these questions a ‘reasonable’ number of

intermediate stages should be shown.

• This is an individual assignment and must be your own work. You must not copy work

from other students. You can ask for help on the MAS286 discussion board, but must

not ask for help on any other internet discussion forum, or email list or anything of a

similar nature. Where we judge that plagiarism has occurred or two pieces of work are

too similar, we may award zero for those assignments.

1

Intravenous bolus doses

These questions are worth 35 marks.

1) A drug is delivered by intravenous bolus. The body can be considered as a single

compartment for this drug. The half-life of the drug is 5 hours, the effective volume is 25 L

and the initial dose is 250 mg. Assuming no further doses are given, after how long (to the

nearest hour) will the concentration of the drug in the patient have reached 2.5 mg/L? (3

marks)

2) Suppose that guidelines for this same drug, with the same elimination rate and effective

volume of 25 L, instruct a maximum concentration of 22.5 mg/L and that a concentration

of 10 mg/L should be maintained for the drug to be effective. The drug manufacturer

suggests that doses of 250 mg should be repeated every 8 hours. Is this dosing regime

consistent with the guidelines, and if not, why not? (6 marks)

3) You are asked to come up with a more effective dosing regime for this drug. Propose a

loading dose, maintenance dose and time interval for maximum effectiveness within the

guidelines. For realism, provide the time interval to the nearest hour and doses to the

nearest 25 mg. Include a plot of the concentration kinetics for 48 hours and describe the

behaviour. (15 marks)

4) A different drug spends a significant amount of time moving between the bloodstream (C)

and tissues (D), and as such a two-compartment model is more appropriate. Assume the

elimination rate from the bloodstream is now found to be k = 0.2 hr−1

, and the transition

rates in to the tissues, a = 0.75 hr−1

, and out of tissues, b = 0.8 hr−1

. A patient with an

effective bloodstream volume of V = 15 L is given a single intravenous bolus dose of the

drug. After 10 hours the concentration of the drug in the tissues is found to be 5.49 mg/L.

What dose of drug was the patient given? (11 marks)

2

Oral doses

These questions are worth 35 marks.

5) A drug is delivered orally, first reaching the gastrointestinal tract where it is absorbed in to

the bloodstream. Suppose a dose of 200 mg is given to a patient in a single dose. After

one hour the amount of drug in the GI tract is 50 mg. Find the rate of absorption out of

the GI tract, a, to three decimal places. (2 marks)

6) This same drug, again with an initial dose of 200 mg, has a rate of elimination from the

bloodstream of k = 0.15 hr−1

and the effective volume is V = 20 L. To the nearest

minute, how long after the dose is administered will the maximum concentration of the

drug occur, and how much will that concentration be to three decimal places? (5 marks)

7) The guidelines for this drug state that its concentration should be kept above 15 mg/L to

be effective, and that the average concentration between doses should be 25 mg/L.

Propose a dose amount and time interval for maximum effectiveness within the guidelines.

You may assume that absorption is negligible at later time points. For realism, provide the

time interval to the nearest hour. Include a plot of the concentration kinetics for 48 hours

and describe the behaviour. (13 marks)

8) A different drug, which is also administered orally, is found to have identical absorption and

elimination rates, i.e. a = k. Explain why the solution for the drug concentration used in

the previous parts cannot be applied here. Setting a = k and C = XB/V , use the

equations for the dynamics

dXG

dt = −kXG,

dXB

dt = kXG − kXB

to find a general solution for the concentration, C(t), (with initial conditions XG = XG(0)

and XB = 0). Find the concentration of the drug in the bloodstream after 3 hours, to two

decimal places, if k = 0.1 hr−1

, XG(0) = 200 mg and V = 25 L. (15 marks)

3

Intravenous infusion doses

These questions are worth 30 marks.

9) A drug is to be delivered in to the bloodstream by an intravenous infusion at a constant

rate. It is recommended that a patient reach a ‘steady-state’ concentration of 20 mg/L.

The half-life of the drug is 5 hours and the effective volume is 25 L. What should the

infusion rate r be (to the nearest 10 mg/hr)? (9 marks)

10) A drug has been given at a constant infusion rate of 250 mg/hr for one hour. Two drug

concentration values, determined at 2 hr and 6 hr after the start of the infusion, were 4.5

mg/L and 2.8 mg/L respectively. Find the elimination rate and effective volume, to three

decimal places. (9 marks)

11) A drug is to be delivered via repeated intravenous infusions, each lasting for 30 minutes.

The drug has a rate of elimination from the bloodstream of k = 0.2 hr−1

and the effective

volume is V = 30L. The guidelines for this drug state that its concentration should be kept

above 10 mg/L to be effective, and below 25 mg/L to avoid overdosing. What is the

longest we can wait between infusions to ensure that the drug is administered safely and

effectively (to the nearest hour), and what should the infusion rate r be (to the nearest 10

mg/hr) for this regime? Include a plot of the concentration kinetics for this regime for 24

hours and describe the behaviour. (12 marks)

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