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


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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

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