**4. Elimination or excretion of drugs and adverse effects**

It should be noted that there are variations in the concentration of the elements and molecules making up the body. These variations are rhythmic, cyclic, and dependent on the age, sex, and health status of the individuals. It is known that, in each disease state, and in case of multi-morbidity, the composition of these elements and molecules vary in relation to the lifestyle of an individual, namely his/her water and food intake, smoking and alcohol consumption, exercise and sleeping patterns in terms of quantity, quality, and variety or diversity [21–24]. This situation largely explains why a same dose of a drug may not always produce similar effects (beneficial or adverse) on a group of individuals even if they have same bodyweights, are of same ethnicity or sex. This observation explains why standard doses cannot be prescribed indiscriminately to each individual patient; hence the new concept of individual-

**Figure 4.** Body composition. Source: Fomon et al. [19]; Chumlea et al. [20].

6 Pharmacokinetics and Adverse Effects of Drugs - Mechanisms and Risks Factors

The need for individualized regimen can be more understood when one considers the "halflife" concept. Half-life is a very useful parameter in pharmacokinetics; it is defined as the time it takes for the concentration of a drug to halve from its initial peak concentration in plasma or urine. It is important to note that even drugs from the same class have different half-lives because they have different volumes of distribution and/or systemic clearance. This is so because the apparent volume of distribution depends, as said earlier, upon the nature of the drug and the makeup of individuals. For instance, lipophilic drugs tend to have large apparent volumes of distribution and to be widely distributed in someone who is obese, due to the availability of more adipose tissue. Hence, the lipophilic drugs will have a longer elimination half-life in obese people; their longer stay may mean also longer lingering affects both

When drugs accumulating in other compartments continue to be taken, there will be a saturation of the receptors or even storage spaces in these compartments, resulting in much more concentrations in the interstitial liquids, and overwhelming of related receptors, thus the advent of adverse and side effects not typical of drug class. Such side effects may and should become a subject of pharmacovigilance investigation. It should be said here that atypical or new side effects may occur even with normal doses in certain individuals because of their uniqueness with regard to the receptors, enzymes, or proteins, they may have in abundance or absence thereof as a matter of their genetic makeup or as a result of a subclinical or clinical

ized treatment regimen.

beneficial and unwanted [23, 25, 26].

Once a drug is metabolized and reduced to hydrosoluble entities, it is ready to be excreted through the kidneys and eliminated in the urine. However, some changes may impact negatively to this process. An important pharmacokinetic change in the elderly, for instance, is the decrease in renal drug elimination due to the fact that as someone ages, his/her renal mass as well as glomerular filtration and tubular secretion capacities decrease. It should be noted that after age 40, there is a decrease in the number of functional glomeruli, and the renal blood flow is estimated to decline by approximately 1% yearly. The clinical effect of decreased renal clearance includes prolonged drug half-life, increased serum drug level to toxic level which obviously leads to increased potential for adverse drug reactions [6, 31].
