**9. Dosage and effect**

A particular dose of an administered drug is subject to the biochemical processes in the body as shown in Figure 5. The desired effect of a drug is proportional to the concentration of the drug at its site of action which is described by the following kinetic parameters: (i) The apparent volume of distribution (Vd) which is the volume of the hydrophilic and hydrophobic spaces in the body that the drug is distributed in. It is obtained by dividing the injected dose (Do) by the initial concentration (Co) in blood plasma. Drugs that bind to tissues extensively exhibit low concentrations in the plasma and therefore, have higher a Vd compared to those that are mainly bound by blood plasma proteins. An average 70kg person has a total body water volume of ~ 50L of which ~ 10L occupy extra-cellular space.

**ii.** Drugs which do not readily dissociate from their receptors. In this case the pharma‐

**iii.** Drugs which combine with receptors and irrespective of their rates of association/

Drug disposition process most of the times follows the 1st order kinetics in which disposition is proportional to the concentration of the drug at any given time. Therefore, the concentration of a drug in plasma will decrease at a rate that is proportional at all times to the concentration

> = In[C] ct co

eIn [C]t [C]o

> [Ct ] [Co]

A more convenient form of this equation is obtained by taking log10

Kt

e-Kt

= e-Kt

=

In[C]t In[C]o - = Kt or InC = InCo - Kt

A linear relationship is obtained when the logarithm of concentrations (log10C) is plotted

ln *x* = 2.303log10 *x* (1)

dissociation sets in motion a cascade of events which runs on despite falling plasma

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cological effect persists despite the falling plasma concentration.

concentrations.

itself. Therefore;

*dt* = K C

*<sup>C</sup>* <sup>=</sup>*∫Kdt* 


Since

It follows that;

2.303log10 C = 2.30.3log10 C0 - Kt

2.303

against (t), times of observation (Figure 6).

and log10 C=log10 C0 - *Kt*

*∫* -*d C*

**10. Kinetics of drug disposition process**

**Figure 5.** Drug disposition routes from absorption to excretion

The apparent volume of distribution cannot tell us where in the body the drug really is. The (Ctox) is the maximum drug concentration beyond which there would be toxic effects in the body, while the (Cther) is the plasma concentration of a drug that would achieve a therapeutic effect or effective clinical response. The steady state concentration (Css) is that concentration that should be maintained between any two drug administration intervals. These pharmaco‐ kinetic data are important in that they characterize the fate of drugs in the body and are required by pharmacologists to calculate doses and frequencies of drug administration. However, in some clinical responses, the intensity of pharmacological action correlates better with the concentration of free drug in plasma, while in other responses there is no direct relationship between drug concentration and clinical response. The main variations of the drug response effects include;

**i.** Drugs which combine with their receptors as quickly as they dissociate from them; for this category of drugs, the pharmacological effect increases or reduces in tandem with the plasma drug concentration.

