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Number of Pages: 4 (Double Spaced)
Language Style: English (U.K.)
Writing Style: APA
Number of sources: 4
Answer both questions. Total marks: 100
1. 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 the best way for the pharmacists to proceed.
50 marks
2. During a clinical trial, 60 mg of a drug X is given intravenously to a volunteer, and plasma samples taken every two hours are analysed. The data obtained are shown in Table 1.
Table 1. Plasma concentrations of drug X in volunteer
Time /h Plasma Concentration (Cp) /mg L-1
2 10
4 6.7
6 4.5
a) On semi-log (i.e. log Y axis) graph paper plot the data above, and label accordingly.
10 marks
b) Estimate the initial plasma concentration Cp(0) at time zero.
5 marks
c) ?and using this, calculate the volume of distribution for drug X.
5 marks
d) What does this tell us about the physicochemical nature of Drug X?
5 marks
e) Why can Vd be a useful parameter for a prescriber?
5 marks
f) Estimate graphically the half-life of the drug in this person.
5 marks
g) Calculate the elimination rate constant Kel .
5 marks
h) Now calculate the clearance of drug X in this person.
5 marks
i) Explain in words what your answer to (h) means.
5 marks
Formulae for Q2:
Vd = Q/Cp(0) Kel = CL / Vd t?=0.693/Kel
Where:
Vd = volume of distribution
Q = dose
Cp(0) = plasma concentration at time zero.
Kel = elimination rate constant
CL = clearance
t? = half-life
