Toxicity studies preclinical data

Indirect Immunotoxic Effects. A problem related to data interpretation is how to distinguish secondary effects that may indirectly result in immunotoxicity from the primary effects of immunotoxicity in preclinical toxicity studies. Various factors may produce pathology similar to that of an immunotoxin ... 

The Indian regulatory system requires submission of reproductive toxicity study data in animals in support of Phase II and Phase III clinical trials. Table I provides all preclinical data that are required for the various phases of clinical studies. 

In order to facilitate clinical development, it is important to define risk and benefit in the most reasonable and appropriate way. Preclinical studies are the foundation for the initial and ongoing assessment of potential risks and as such should be designed in order to realize their maximum value. The primary objective of preclinical safety evaluation studies is to provide data that clinical investigators can use to better predict adverse effects in study subjects and to help researchers design clinical studies that will minimize their occurrence. The same information will also help to guide research toward new, less toxic drugs and, if harmful effects cannot be entirely avoided, to suggest means to lessen or alleviate the adverse actions. 

The pharmacokinetic profile of a product or substance describes its fate in the organism with respect to the absoption, distribution, metabolism and elimination. For chemical compounds pharmacokinetic data form the basis for an assessment of pharmacodynamic and toxic effects and allow a rationale for a dosage regime to be established for preclinical and clinical studies. 

Preclinical pharmacokinetic (PK) studies provide information useful for supporting efficacy and safety evaluation studies in animals, preclinical and clinical study designs, dosing regimen development, and interpretation of toxicity data. These studies provide PK data that may be useful in dose escalation in healthy volunteers and patients. Toxicokinetics is a major component of toxicology studies. It enables the investigation of the relationship between drug dose and measured concentration, primarily the establishment of the dose proportionahty and hnearity or nonlinearity in pharmacokinetics. 

Exposure multiple or exposure ratio is a common term used in the pharmaceutical industry to describe the fold of exposure of Cmax or AUC observed at doses used in toxicity studies, compared to the Cmax or AUC at the highest marketed dose in humans or projected therapeutic dose based on preclinical data. This number provides an estimate for the safety margin of a compound and is helpful for guiding the dose selection of drug safety studies. 

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