Embedded Files
teratogenic and mutagenic affects, that is their potential to cause adverse effects on the foetus and genetic material, respectively. • To determine how the animal handles the drug: How is it absorbed? How is it metabolized? How long does it take to eliminate the drug from the body? At the end of the preclinical testing, some chemicals are discarded for the following reasons: • The chemical lacks therapeutic activity when used with living animals. • The chemical is too toxic to living animals to be worth the risk of developing into drugs. • The chemical is highly teratogenic or mutagenic. • The safety margins are so small that the chemical would not be useful in the clinical setting. FIGURE 1.1. Phases of drug development. All chemicals that theoretically may have therapeutic activity Drugs dropped from study Drugs that 1. Lack therapeutic activity 2. Are too toxic; teratogenic 3. Have a small safety margin Drugs that 1. Lack therapeutic activity in humans 2. Are too toxic 3. Produce unacceptable side effects Drugs that 1. Are less effective than expected 2. Are too toxic 3. Produce unacceptable side effects 4. Have a low benefit-to- risk ratio 5. Are not as effective as available drugs Drugs that 1. Produce unacceptable side effects 2. Produce unexpected responses Drugs cleared for human testing Drugs cleared for limited clinical studies Phase IV continued evaluation Drugs cleared for large scale clinical studies Drugs approved for marketing by regulatory authorities Preclinical tests of efficacy and toxicity Phase I studies Phase II studies Phase III studies SAMPLE phase I, the variay have therapeutic herapeutic d laboratory animals. important part of the drug develthere is signifi cant public opposiin experiments. A comment often experiments. A comment often tho tweighed tweighe Defence Society, the number of experiments the number of ased by over 35% in the p sed by over 35% in the 2009). have several purposes: several purposes: are likely to have benefi have benefi cial effects in disease. evaluate any toxic effects in the short and long term. assess their teratogenic and assess their teratogenic mutagenic affects, that is their potential to cause adverse effects on the foetus and potential to cause adverse effects on the foetus genetic material, respectively. genetic material, respectively. To determine how the animal handles the drug: absorbed? How is it metabolized? How long to eliminate the drug from the body? At the end of the preclinical testing, discarded for the following reasons: discarded for the following • The chemical lacks therapeutic The chemical living animals. • The chemical is too to The chemical is to the risk of developing • The chemical is • The safety margins not be useful All chemicals that theoretically may have therapeutic activity Drugs cleared for human testing SAMPLE Drugs that 1. Lack therapeutic activity Drugs dropped from study Preclinical tests of efficacy toxicity CHAPTER 1 — Introduction to Drugs 7 Some chemicals, however, are found to have therapeutic effects and acceptable safety margins. This means that the chemicals are therapeutic at doses that are reasonably different from doses that cause toxic effects. Such chemicals will pass the preclinical trials and advance to phase I studies. Phase I Studies Phase I studies are the fi rst occasion where the drug is tested on humans and the aim is safety evaluation not effectiveness in disease control. Permission to enter phase I studies must be granted by the local ethics committee and also the National Drug Regulatory Authority. The ethics committee will evaluate the risks to the volunteers, the process of recruiting volunteers, the experience of the clinical investigators and the design of the study. The regulatory authorities will determine if there is a scientifi c need to carry out the study. The overriding authority in control of this regulatory procedure is the Medicines and Healthcare products Regulatory Agency (MHRA) . In phase I studies small groups of between 40 and 60 individuals volunteer to test the drugs. These studies are performed by specially trained clinical investigators. The volunteers are fully informed of possible risks and are paid for expenses and for any inconvenience caused. Generally, the volunteers are healthy,
Report abuse