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Has anyone been asked to conduct a bioequivalence study of similar IV
Reference Form 1 = water soluble drug lyophilized from water with
small amount of NaOH to adjust pH
Test Form 2 = water soluble drug lyophilized from water with some
sucrose (mg sucrose ~ = mg drug) and sodium phosphate dibasic buffer
and small amount of NaOH to adjust pH
Test Form 3 = water soluble drug crystallized from aqueous solution
containing about 5% calcium
All are reconstituted in 10 ml normal saline and administered at 50 mg/
mL by rapid infusion or further diluted with saline or Ringers lactate
and administered over 30 minutes
Safety and tolerability are assumed to be similar.
Thanks - dave
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Bioequivalence is an estimate of relative bioavailability. The
concept is meaningless for i.v. infusions, because all solutions have
100% absolute bioavailability - there's nothing relative. Any ratio
you get is a measure of how consistently you set up the infusion and/
or the relative amounts in the stock solutions.
If your ratios of AUC and Cmax are not around 1.00? No problem, just
put more in the bag and adjust the infusion rate.
The PK parameters of AUC and Cmax are meant to estimate the rate and
extent of absorption - they are inappropriate for i.v. infusions.
So what's left? Good question. Perhaps you should consider the DME
part of ADME - how do the solutions match each other with respect to
volume of distribution, clearance, half-life and binding constants at
the target molecule. In other words, once the drug enters the system
(100% of the time) does it behave like the reference and it is treated
like the reference?
What do the rest of you think?
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