There are no absolute
rules governing the size of the first dose
administered to humans. The FDA has recently
issued guidance on estimating Maximum Safe
Starting Dose (MRSD), which is assessed
from the NOAEL from pre-clinical studies.
The Human Equivalent Dose (HED) is calculated
using body surface area conversions, generally
MRSD is 1/10th HED. However there are occasions
when BSA conversions are not appropriate.
Each dose increment is typically two-fold,
but less aggressive regimens may be appropriate
for classes of drug that may cause life-threatening
toxicity, as is the case with anti-arrhythmic
compounds, for example. |
