Fundamentals of Medicinal Chemistry

(2) Substitute this value in Equation (8.28) to give the absolute bioavailability:

absolute bioavailability¼

5 : 01 = 50

3 : 96 = 30

¼ 0 : 76

This value indicates that the IV bolus administration gives a significantly better

bioavailability than oral administration.

(6) The parameters that could be used to compare the biological activities of the

analogues are the following.

Half-life(calculate using Equation (8.5) ), which would give a measure of the

duration of the action. The longer the half-life the longer the time the drug is

available in the body.

Absolute bioavailability(calculate using Equation (8.28) ). The bigger the absolute

bioavailability the greater the chance of a favourable biological action.

Analogue: A B C D

Half-life (minutes): 5 25 15 40

Absolute bioavailability: 1.036 1.526 0.812 1.175

The best analogue is D because it has the longest half-life and a reasonable

bioavailability.

(7)Css¼k 0 /Clpand Clp¼Vdkel

Calculatekelfrom the value oft1/2(use Equation (8.5) ).

t 1 = 2 ¼ 0 : 2772 h^1

ConvertVdto cm^3 and calculate the value of Clp. Substitute Clpin the expression

forCss. Answer: rate of infusion¼4.35mgcm^3 h^1.

Chapter 9

(1) (a) See Section 9.1. (b) See Section 9.8.1 and 9.8.2.

(2) See Section 9.1.2. and 9.1.4.

(3) See Section 9.2, especially Table 9.1.

268 ANSWERS TO QUESTIONS