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I have a compound that was administered as a single IV bolus dose to
mice, rats, and dogs (3 different dose levels were tested, n = 3-5/
dose group). Much to my surprise, the plasma concentration versus
time profiles for all doses in rats and dogs presented a Cmax around
2 hr (rats) to 6 hr (dogs) postdose. The profiles in mice, on the
other hand, were consistent with an IV bolus administration.
Initially, I thought that maybe the vein was missed during the
administration, but I don't believe this mistake would have been made
in all animals and at all dose levels. In addition, each species was
handled by a different person, at different study sites, so it is
very unlikely that this was an administration mistake.
I cannot disclose much information about the compound, except that it
has a lipid-like structure, and a considerably long half-life (> 24
hr in dogs). Could it have precipitated in the blood? What are other
possibilities? Can anyone provide any insight (and references)?
Thanks in advance.
Edgar L. Schuck, PhD
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I have a few questions to ask.
Q1. Was the formulation given as a true solution?
Q2. Was the dose given as a bolus or as infusion? For how long was
the dose given?
Q3. What was the volume of the dose given across the species?
Q4. Did the person (who administered the dose in mice) also
administer at least one dose in rats and dogs too? This could have
crosschecked whether the other people are giving the injection properly.
It's very unusual to see a pattern like this with IV dosing. I would
suggest going back and checking all procedures critically.
Hope this helps
Manish Issar Ph.D,
Eon labs Inc., Wilson, NC
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