Drug development animal testing

Preclinical drug development also involves animal testing [61]. Data from one rodent species and one nonrodent species are usually collected to determine the absorption, metabolism, and toxicity characteristics of the compound. Both short-term (2 weeks to 3 months) and long-term (up to several years) studies are done. The long-term studies are particularly useful for... 

Rifaximin is broad-spectrum antibiotic, which covers many skin pathogens, whose lack of transcutaneous absorption has been well documented by both animal [8] and human [9] studies. On these grounds, a topical formulation (i.e. cream) containing 5% of the active compound was developed and tested in the treatment of pyogenic skin infections. Some open trials [20, 21] showed the efficacy and safety of the formulation and pointed out the lack of selection of resistant strains after topical application of rifaximin. In any event, drug delivery from the topical formulation is orders of magnitude higher than the... 

The costs of drug development increase as a drug progresses through the development pipeline. Preclinical development is the time when chemical compounds are tested in the laboratory to learn as much as possible about how medicines work "in a test tube." These types of experiments can be done with many compounds in a relatively short time and with relatively low cost. This is also the time that animal testing begins to see whether the chemical compounds are safe. These studies help scientists to determine how medicines will be dosed in humans. They are also important to understand whether any toxicity is related to the medicines. Toxicological tests are time... 

Drug development is a long and cost-intensive business. Only after years of lead identification, chemical optimization, in vitro and animal testing can the first clinical trials be conducted. Unfortunately, many projects still fail in this late stage of development after a considerable amount of money has been spent. According to estimates, preapproval costs for a new drug exceed US 800 million [1]. 

Drug Development Tests are performed on the lead compounds in test tubes (laboratory, in vitro) and on animals (in vivo) to check how they affect the biological systems. The tests, often called preclinical research activities. 

The use of animals for pharmacological and toxicological studies has yielded invaluable information for drug development. However, many drug candidates failed in Phase I and II clinical trials because the animal models were insufficient to represent human systems and functions for some drugs. Efficacy and acceptable toxicities derived from animal models were not replicated in humans (Exhibit 5.8). In recent years, the direction in development of drugs has shifted toward the use of ex vivo, in vitro assays and even in silico methods. Nevertheless, some tests must stiU be confirmed in animals. 

In vitro assays are increasingly being used. Some of the reasons are cost, availability of more rapid results, and avoidance of negative publicity. Assays such as cytochrome P-450 enzymes, the Ames test, and the mouse lymphoma tk test are in vitro methods. For absorption studies, Caco-2 (Exhibit 5.9) and Madin-Darby canine kidney cell assays are now routinely used. Hepatocyte cell lines with metabolism capacity are being developed to test drug metabolism and toxicity. All these examples show that, where possible, pharmaceutical firms are gradually dispensing with animal studies. 

Potential new drugs that show acceptable toxicity in animals are usually first tested in healthy human volunteers before being investigated in patients. Chapters 3-6 deal with these aspects of new drug development, and it is the purpose of this chapter to consider how safety should be evaluated at the time of the product licence application and in the post-marketing phase. 

---