I try to calculate PDE for cefdinir based on the results of reproduction and developmental toxicity studies as in the attachment. According to EMA guideline, the equation used to calculate PDE is:
PDE = (NOAEL x Weight Adjustment) / (F1 x F2 x F3 x F4 x F5)
with:
F3 = A variable factor to account for toxicity studies of short-term exposure
F3 = 1 for studies that last at least one half lifetime (1 year for rodents or rabbits; 7 years for cats, dogs and monkeys). F3 =1 for reproductive studies in which the whole period of organogenesis is covered.
F3 = 2 for a 6-month study in rodents, or a 3.5-year study in non-rodents.
F3 = 5 for a 3-month study in rodents, or a 2-year study in non-rodents.
F3 = 10 for studies of a shorter duration.
In all cases, the higher factor has been used for study durations between the time points, e.g., a factor of 2 for a 9-month rodent study.
F4 = A factor that may be applied in cases of severe toxicity, e.g., non-genotoxic carcinogenicity, neurotoxicity or teratogenicity. In studies of reproductive toxicity, the following factors are used:
F4 = 1 for fetal toxicity associated with maternal toxicity
F4 = 5 for fetal toxicity without maternal toxicity
F4 = 5 for a teratogenic effect with maternal toxicity
F4 = 10 for a teratogenic effect without maternal toxicity
Which value of F3 and F4 are appropriate to the result of studies?
Hello Hong,
You have given four different studies here for Cefdinir. Ideally, the lowest NOAEL/LOAEL available value should be taken, if several values are available.
-Here, taking LOEL of 10 mg/kg/d for calculation of PDE, values of safety factors will be F3= 1 (whole period of organogenesis is covered), F4= 1 (they have mentioned matenal toxicity but nothing about fetal toxicity, but they mentioned it as non-teratogenic also )
-If you go for the LOEL of 1000 mg/kg, then F3=10, F4=1
-If you go for LOEL of 32 mg/kg, then F3=1 (whole period of organogenesis is covered), F4=5
- Badges
- Science topic
- Similar topics
- Clinical Pharmacology
- Dosing