**14.5. Phase III clinical trials**

The drug is evaluated in a much larger number of patients (thousands) to further establish safety and efficacy. Phase III trials are performed in settings similar to those anticipated for the ultimate use of the drug. After successful phase III trials, the next step is the application for review of the new drug to seek approval to use the drug for clinical management of the disease condition.

#### **14.6. Phase IV clinical trials** The drug is evaluated in a much larger number of patients (thousands) to further establish safety and efficacy. Phase III trials are performed in settings similar to those anticipated for the

*Phase IIIclinical trials* 

*Phase IV clinical trials* 

candidate extract

This phase is concerned with post-marketing surveillance and the main goal is to as‐ sess adverse reactions, patterns of drug utilization, discovery of additional indications. The interrelationships between the various studies in drug development are illustrated in Fig 13 below; ultimate use of the drug. After successful phase III trials, the next step is the application for review of the new drug to seek approval to use the drug for clinical management of the disease condition.

between the various studies in drug development are illustrated in Fig 1.13 below;

This phase is concerned withpost-marketing surveillance and the main goal is to assess adverse reactions, patterns of drug utilization, discovery of additional indications.The interrelationships

Phase II clinical trials include inert placebos as negative controls and older active drugs as positive controls alongside the investigative compound. These studies are done in special clinical

**14.7. Pharmacogenomics and drug development**

some, a phenomenon known as gene duplication.

**14.8. Individualized drug therapy**

choosing a drug regimen.

tiate new discovery programs for other pharmaceutical compounds.

duce a desired therapeutic effect with minimum toxic effects.

**i.** Dose of the drug to be used and the formulation.

The regimen is described in terms of the following:

**ii.** Frequency with which it is administered.

**iii.** Route of drug administration.

logical level of patient (Figure 14).

The personalized medication which takes into account the genetic make-up of individu‐ als is known as pharmacogenomics. The pharmacogenomic differences that determine in‐ dividualized therapy include genetic polymorphisms of drug transporters, drug receptors, and drug metabolizing enzymes. For example, genetic variation in Cyt P450 en‐ zymes that are largely responsible for drug metabolism shows that different individuals respond differently to drug efficacy or toxicity. Genetic variants in the drug target, the disease pathway, genes or drug metabolizing enzymes could all be used as predictors of drug efficacy or toxicity. For example, drug monitoring using perpherazine, a Cyt P450 substrate, shows that there are three main categories of individuals; the efficient metabo‐ lizers obtained from the heterozygotes, the poor metabolizers from the homozygotes and the ultra-rapid metabolizers which carry two or more active genes in the same chromo‐

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The information obtained from pharmacogenetic studies can be used to design new drugs that take the persons' genetic profile into consideration. The most common type of genetic variation are single nucleotide polymorphisms, therefore, a high resolution of sin‐ gle nucleotide map may expedite the identification of genes for various diseases. The molecular profiles of patients identified in phase I and II clinical trials as likely non-res‐ ponders to the putative drug under investigation might present an opportunity to ini‐

Clinical usage of drugs requires a basic understanding of the pharmacokinetic and pharma‐ codynamic drug processes and an appreciation that a relationship does exist between the pharmacological effect or toxic response to a drug and the concentration of the drug. The interpatient and intrapatient variation in disposition of a drug must be taken into account in

A drug dosage regimen therefore is a recipe for the administration of a drug so as to pro‐

The factors that determine the relationship between the prescribed drug dosage and drug effect operate at three levels; prescription level, drug administration level and at the physio‐

**Figure 13.** Illustration of the key steps in the development of a drug from a putative drug candidate extract

**Figure 1.13**Illustration of the key steps in the development of a drug from a putative drug
