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The following message was posted to: PharmPK
Dear All,
We have performed a pharmacokinetic study of ketoprofen in juvenile
pigs after administration of the racemate. The concentrations of the
R- and S-enantiomers in plasma were quantified and we have detected
substantial differences between the AUC of the R- and the S-
enantiomers. We are aware of that one needs to administer the
individual enantiomers to be able to detect and quantify chiral
inversion. We have not done this, but is it possible to get an
indication of the occurrence of chiral inversion by analyzing the
pharmacokinetic parameters after the administration of racemic
ketoprofen?
Thanks in advance!
Best regards,
Torunn Fosse
Ph.D. student
Norwegian School of Veterinary Science
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The following message was posted to: PharmPK
Dear Torunn
You have already answered to your question. You cannot get an indication
or a proof that chiral inversion takes place in the body just by PK
analysis (modelling) of R- and S-ketoprofen concentration data after the
administration of racemic ketoprofen!
But you can assume that this inversion happens and under that assumption
you can build a more complex PK model and describe the kinetics of this
process. And with your diagnostic tools you might find that such model
describes your data better. However, your model is right as much as this
assumption is right (by the way, the same problem arises when assuming
that the volume of distribution is the same for R- and S-ketoprofene).
So you might need to support the assumption of the chiral inversion;
maybe you can find such information from the data in the literature or
from your >in vitro< findings. You have obviously used an
enantioselective method for the determination of R- and S-ketoprofen
concentrations. So you must have an optically pure ketoprofene standard.
Was the stability of standard solutions of optically pure standard good
over a longer period of time? Did you test the stability of plasma
solutions of pure S- or R- ketoprofen over a longer period of time?
I hope this helps.
Igor Locatelli
Ph.D. student
University of Ljubljana, Faculty of pharmacy
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The following message was posted to: PharmPK
Dear Torunn,
First, talk to your chemist and find out whether based on the
structure chiral inversion is a possibility; in many cases is not.You
can do some simple experiment to get further insight into this by
incubating under acidic or basic conditions (or in the presence of
plasma or blood)
and determining the recovery of the R
and S enantiomers. Do you have data in other species? You may be
deleting with sterospecific PK (e.g., absorption and/or metabolism)
Rostam
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