Fundamentals of Medicinal Chemistry

Table 8.3 The hepatic extraction values of some drugs

DrugEHvalue<0.3 (low) DrugEHvalue 0.3–0.7 DrugEHvalue>0.7 (high)

Antripyrine Aspirin Cocaine

Diazepam Codeine Lignocaine

Nitrazepam Nifedipine Nicotine

Warfarin Nortriptyline Propranolol

a specific region of the body, to be taken into account when assessing the

pharmacokinetic behaviour of the drug in that region of the body (see section

8.5). Clearance values enable the medicinal chemist to compare the effect of

structural changes on drug behaviour and as a result decide which analogues

might yield drugs with the desired pharmacokinetic properties. Extraction ratios

can also be used to link the required desirable characteristics of a potential new

drug with the chemical structures of the analogues of a lead. Their use can lead

to the avoidance of the loss of a potential drug by indicating the most effective

dosage form.

8.4.3 Intravenous infusion

In intravenous infusion, the drug is infused into the vein at a steady rate. Initially,

the plasma concentration of the drug increases as the amount of the infused drug

exceeds the amount of the drug being eliminated (Figure 8.7). However, as the

concentration of the drug in the plasma increases, the rate of elimination

also increases, until the rate of infusion is equal to the rate of elimination, at

which point the concentration of the drug in the plasma remains constant. As

long as the infusion rate is kept constant, the drug plasma concentration will

remain at this steady state level (Css). When infusion is stopped the drug

Time t

Cp Infusion

started

Infusion

stopped

Css........................

Steady state

Figure 8.7 Plasma concentration changes with time in intravenous infusion

INTRAVASCULAR ADMINISTRATION 169