Dose range-finding study

A dose-range finding study in pregnant animals is recommended to aid in dose selection for the main study. Typically, six mated animals per group are used for dose-range finding investigations. 

A typical dose range-finding study comprises 24 dams divided across four groups (three treated plus one control). 

Preliminary, or dose range-finding, studies are recommended in order to determine appropriate doses to be used in the main teratology investigation. Although data are generally available from repeat dose toxicity studies, i.e., 2 or 4-week investigations, unwanted surprises can be avoided in a main study by first admin-... 

A typical full teratology study in the mouse is comprised of 100 dams divided across four groups (three treated plus one control) with the aim of attaining at least 16 litters per group for evaluation. The dosing period (at least between days 6 and 15 post-coitum) and the maternal observations are the same as those described for a dose range-finding study. 

The dosing period, from day 11 through to at least day 35 post-coitum and the maternal observations, are the same as those described for a dose range-finding study. 

Each candidate compound for entry into development was tested in FETAX. The objective was to give an early alert for developmental toxicity. A standard development plan was followed when FETAX gave negative results. In the case of a positive FETAX result, the mammalian embryo-fetal toxicity studies (preceded by dose-range finding studies) were brought forward (i.e., just after the regulatory repeat-dose toxicity study in rats). 

Based on preliminary (dose range-finding) study results " Results fi om a mouse study Positive result, previously foimd inconclusive... 

In the cases where only dose range-finding studies were performed and gave positive results, the routine external examination of the fetuses was supplemented with a detail fresh internal examination for rabbits, or fixed visceral and/or skeletal examinations for rats. These dose range-finding studies were thus sufficiently sensitive to detect strong teratogens. 

Pharmacology experiments Basic research Dose-range finding studies Studies to develop new methodologies... 

Singh AN, Beer M. A dose range finding study of buspirone in geriatric patients with symptoms of anxiety. J Ctin Psychopharmacol 1988 8 67-68. 

The MTD is generally chosen based on data derived from toxicity studies of 3 months duration. Testing options for dose-range-finding studies are as follows ... 

Another phase of the Hackett et al. (1987) study investigated the potential teratogenicity of lewisite in rats. In this phase of the study, no maternal toxicity or teratogenic effects were observed, thereby identifying 1.5 mg/ kg as a NOAEL. However, it must be noted that in a dose range-finding study in rats (Hackett et al., 1987 see Section 3.3), doses of 2.0 mg/kg and 2.5 mg/kg resulted in 10% and 20% maternal mortality, respectively. 

The MTD is mostly defined in a 3-month dose-range-finding study, allowing optimal dose setting for the pivotal chronic bioassay. 

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