Repeated dose toxicology studies

Evidence of immunotoxicity in repeat dose toxicology studies ... 

Table 13.10 illustrates examples of functional endpoints that have been successfully incorporated into toxicology studies. The examples cover primarily, but are not limited to, the vital organ systems (i.e., cardiovascular, respiratory, and central nervous systems). The repeat-dose toxicology studies offer an ideal opportunity to compare the pharmacological... 

It is essential to perform preliminary studies if there is no data available in the minipig from repeat dose toxicology studies. 

In most standard development programs, no investigations have been carried out to define the maternal toxicity whether, for example, stress hormones have been increased. If there is reason to believe that maternal toxicity is an important factor, then the submission documents should contain a comparison with the toxicity seen in the repeat-dose toxicology studies and the doses at which the toxicity occurred. If reproductive effects have been found at doses below those found to induce demonstrable toxicity in the repeat-dose studies, care should be taken in concluding that maternal toxicity has been a factor. In this context, the possibility of differences in sensitivity between pregnant and nonpregnant animals should also be considered. 

Twenty-eight-day repeated-dose toxicology studies in two nonhuman animal species. 

The usual GLP 30- or 60-day repeat-dose toxicology study with a recovery group offers an opportunity to perform a more systematic investigation of the more subtle pharmacodynamic or toxicologic effects of biopharmaceuticals than those endpoints usually incorporated into such protocols. Some of these demand tissue samples, but many involve noninvasive biomarkers that can be carried forward into early phase human studies. These might include CNS assessments, inflammation and immune activation or suppression, cell proliferation or apoptosis in tissue samples, and end-organ toxicities. 

Subchronic 3-month repeat-dose toxicology study (rat and dog)... 

Safety pharmacology-related endpoints are typically evaluated directly in repeat-dose toxicology studies in rodents and nonrodents. These endpoints include (a) GI function - assessment of body weight gain/loss, stool consistency (b) CNS... 

A series of single-dose and repeat-dose toxicological studies were conducted to examine the safety of rhAT administered intrave-... 

Dog Purebred beagle, male and/or female Short term PK, dose selection, 2-week and 1-month single and/or repeated dose toxicology studies, 3-months and 1-year repeated dose toxieology studies... 

It should be noted that the format of renal SP studies differs markedly from that of repeat-dose toxicology studies. A renal SP study typically consists of a singledose administration to conscious animals (usually rat) with compound at levels up to the maximum tolerated dose. Urine is collected over 24 h (this can be split into... 

If a NCE has a renal liability, then DIKI biomarkers should be assessed in repeat-dose toxicology studies, which include histopathology endpoints, rather than in SP studies (Redfem et al. 2013). 

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