Fundamentals of Medicinal Chemistry

(Css) may be calculated using Equation (8.21). This equation, which is derived

from Equation (8.16) is based on the asumption that the initial stage of infusion

follows first order kinetics.

t¼t 1 = 21 :44 ln (1Cp=Css)(8:21)

At the steady stateCp ¼ Cssand so the time taken to reachCsscan be

calculated by substitutingCp/Css ¼ 1 in Equation (8.21). This time is depend-

ent on the half-life value: the shorter the half-life the sooner theCssplateau is

reached. Equation (8.21) also allows one to calculate the time taken to reach the

effective plasma concentration, which is normally taken as being 90%of theCss

value. In this caseCp/Css ¼ 0.9. To reduce the time required to obtain an

effective therapeutic plasma concentration, a single IV bolus injection may be

given in conjunction with an IV infusion. As a result, theCssdrug plasma

concentration is reached almost immediately. However, once the drug enters

the bloodstream it undergoes elimination, no matter what its original source, IV

bolus or infusion. This elimination is compensated for by a build-up in the drug

concentration from the intravenous infusion (Figure 8.8). At any timetthe total

concentration of the drug in the system is the sum of the drug from the IV bolus

and the infusion. Its value is equal to the steady state concentrationCssof the

drug. The net result is that the patient almost immediately receives an almost

constant effective therapeutic dose of the drug.

Time t

Cp

Css

Total dose

Concentration of the drug from the IV bolus dose

Infusion

Figure 8.8 The effect of a single IV bolus on the plasma concentration of a drug administered by

IV infusion

8.5 Extravascular administration

The most common form of enteral dosage form is oral administration. Conse-

quently, this section will mainly be concerned with the pharmacokinetics of

EXTRAVASCULAR ADMINISTRATION 171