Human studies drug toxicity

In studies conducted on diseases mainly affecting pediatric patients, the development will be entirely in pediatric patients. However, in addition to the appropriate usual toxicology and neonate animal toxicology, the first-in-humans studies for toxicity and safety are usually done in healthy adult volunteers. Clearly, however, drugs such as the surfactants would yield no useful data from adult testing. For these unique pediatric situations, new measurements and end points may need to be developed and validated. Frequently, the FDA will involve an advisory panel to help determine what these might be. 

The primary objective of a Phase I trial is to assess the safety of the drug in humans. Studies are normally conducted in healthy male volunteers, although specific categories of subject may be used in certain cases. For example, to avoid the risk of low blood pressure, subjects with mild hypertension would be more appropriate for the evaluation of antihypertensive drugs, while patients are likely to be used in the case of drugs that are expected to produce significant toxic effects (e.g. anti-cancer cytotoxic drugs). Remuneration may be offered for participation in the study. The number of subjects is normally between 10 and 100 people. 

In subacute toxicity studies only the highest rifaximin dose (i.e. 100 mg/kg, corresponding to 25 times the therapeutic dose in humans) induced mild toxic effects (like, for instance, acute gastroenteritis) connected to the topical GI action of the drug [59, 255], A dose-dependent increase of the total cholesterol value was recorded in female animals [255], most likely due to an alteration of biliary acid metabolism consequent to the antibiotic effect on gut flora [256]. 

Most of the data regarding inhalation exposure to chloroform in humans were obtained from clinical reports describing health effects in patients under anesthesia. In some instances, the results may have been confounded by the concurrent administration of other drugs with chloroform or by artificial respiration of patients under chloroform anesthesia. Furthermore, most of the studies did not provide any information regarding actual exposure levels for observed effects. Nonetheless, chloroform-induced effects in humans are supported by those observed in animals under experimental conditions. The human studies cited in the profile provide qualitative information on chloroform toxicity in humans. 

In summary, it has been shown that many marine invertebrates and microorganisms produce toxins which influence the environment (are allomones) and numerous, which are toxic to humans, are drug leads which are indispensable research tools for cell biology studies. 

Experimental models. Comparative studies of toxic phenomena are necessary to select the most appropriate model for extrapolation to humans and for testing and development of drugs and biocides. Taxonomic proximity does not necessarily indicate which will be the best experimental animal because in some cases primates are less valuable for study than are other mammals. 

Unequivocally genotoxic compounds need not to be subjected to longterm carcinogenicity studies. However, if such a drug is intended to be administered chronically to humans a chronic toxicity study (up to one year) may be necessary to detect early tumorigenic effects. In practice, this option has not been used since 1997. Main concern of industry is the lack of historical comparison data. The tumor evaluation was always based on 2 year data. 

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