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Determination of the potential for an investigational drug to adversely affect the immune system is a standard component of nonclinical toxicology studies. Potential adverse immune effects include ...

Power calculations are provided for many of the variables recorded in general toxicology studies. It is hoped that these will help the statistician and scientist to discuss what differences are biologically important. Hypotheses relating to satellite recovery groups (also called off-dose groups) are also discussed.

A questionnaire study on the general opinions toward toxicokinetics in Japan revealed that: most Japanese companies currently perform toxicokinetic studies only when they feel them to be warranted. Most believe, however, that in the future, toxicokinetic studies should be integrated into toxicology studies. In order to support and to make toxicokinetics more effective, basic pharmacokinetic studies are necessary at the earliest stage of drug development. Another questionnaire study revealed that most Japanese companies consider the radiolabeled repeat dose pharmacokinetic studies to be informative and useful. These studies, however, should not be uniformly required for all drugs. Rather, they should only be required under certain conditions. Application of a sensitive new radioisotope technology, radioluminography, was outlined and its usefulness in basic animal pharmacokinetic and metabolic studies was pointed out.

This paper demonstrates how toxicokinetic studies can contribute to the interpretation of toxicology studies by helping the toxicologist dktingukh between thepharmacokinetic and pharmacodynamic factors in dose-response toxicity. It also shows the limitations of plasma concentration data.

The predictive value of animal tests is better than most researchers believe; but use of the wrong animal species may cause failure in predicting toxicity in man. To assess safety of new drugs in man, toxicokinetic studies should be conducted within toxicology studies. Special circumstances when toxicokinetic values are essential are described.

A microcomputer-based system has been developed for the acquisition, reporting, and evaluation of clinical biochemistry and hematologic data. The system consists of an IBM microcomputer interfaced with several peripheral devices. Associated computer programs were developed inhouse and customized for use in animal drug toxicity studies. The system has the following advantages: (1) Data are directly transmitted to the microcomputer via interface devices, thereby minimizing the possibility of data entry errors and eliminating the need for handwritten records; (2) individual animal reports and group summary reports are readily generated; (3) individual animal data and group summary values are routinely compared during the data collection phase against a historical reference range database, and “outliers” are flagged, allowing quick identification of aberrant values or parameters that may have been affected by experimental treatments; and (4) treatment groups are tested in the data evaluation phase against con...