Fundamentals of Medicinal Chemistry

(continued)

(ii) the apparent volume of distribution of the drug,

(iii) the clearance of the drug.

What fundamental assumption has to be made in order to calculate these

values?

(4) The clearance of a drug from a body compartment is 5 cm

3

min

 1

. If the
compartment originally contained 50 mg of this drug, calculate the amount of
drug remaining in the system after 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 minutes if the
volume of the compartment was 50 cm

3

. Plot a graph of concentration against
time and determine the values oft1/2andkelfor the compartment and the drug.

(5) A dose of 50 mg of the drug used in question (3) was administered orally to the

same patient who received the IV bolus in question (3). Plasma samples were

taken at regular time intervals and a graph of plasma concentration against

time plotted. If the area under this curve was 5.01, calculate the absolute

bioavailability of the drug in the patient assuming first order absorption and

elimination. Comment on the value of the figure obtained. You may use the

IV data recorded in question (3).

(6) The data in Table 8.5 is based on plasma concentration–time curves for a

number of analogues of a lead. Calculate the relevant pharmacokinetic

Table 8.4.

Time (hours)

Plasma concentration

(gcm^3 ) Time (hours)

Plasma concentration

(gcm^3 )

1 5.9 4 3.0

2 4.7 5 2.4

3 3.7 6 1.9

Table 8.5.

Analogue

Elimination rate constant

minutes

 1

(m

 1

)

AUC IV bolus (30 mg dose)

gmcm

 3

AUC single oral dose

(30 mg dose)gmcm

 3

A 0.1386 30.4 31.5

B 0.0277 31.2 47.6

C 0.0462 100.3 81.4

D 0.0173 69.7 81.9

(continues overleaf)

QUESTIONS 179