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CB   February 2017
CH5011 Data Handling Coursework
Answer both questions. Total marks: 100

Phenytoin is an anti-epileptic drug. It is a weak acid with a pKa of 8.1 The unionised form is insoluble, and will form a precipitate. Consequently when infusing intravenously (IV) it is important to avoid this from happening.

A pharmacist prepares a phenytoin solution for IV infusion; commonly the pH of infusion solutions is pH 5.0    A colleague suggests they should consider changing the pH of the solution to avoid precipitation.
Using the Henderson-Hasselbalch equation, determine a possible pH range which could be used, also bearing in mind any risks to the patient.
50 marks

A patient with clinical depression is given a dose of 75mg of imipramine, and plasma samples taken at various time intervals are analysed.

The data obtained are shown in Table 1.
Table 1. Plasma concentrations of imipramine.

Time   /h
Plasma Concentration (Cp)    /mg L-1





a) On semi-log (i.e. log Y axis) graph paper, plot the data above, and label accordingly (hint – it will be a straight line as it follows first order kinetics).

15 marks

b) Estimate the initial plasma concentration Cp(0) at time zero.

10 marks

c) …and using this, calculate the volume of distribution for imipramine.

10 marks

d) What does this tell us about the distribution of the drug to the tissues, and what might we infer concerning imipramine’s physicochemical nature?

10 marks

e) Why can Vd be a useful parameter for a prescriber?

5 marks

f) From your graph, estimate the half-life of the drug in this patient.

(This is best done by find the time which elapses between one concentration, and half of that concentration).
10 marks

g) Now calculate the clearance of drug X in this person.

10 marks

h) Explain in words what your answer to (g) means.

5 marks
Formulae for Q2:
VD = Q/Cp(0)     t½=0.693 x VD/CL
VD = volume of distribution
Q = dose
Cp(0) = plasma concentration at time zero.
CL = clearance
t½ = half-life

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