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Dear All
I am curious whether someone has experiences dealing with bell shape
PK. For example, when we escalate dose, AUC increased with
increasing dose levels until certain dose levels. However, AUC
actually decreased after that. I have seen that in pharmacodynamic
assessment but it is really the first time that I see in
pharmacokinetic assessment. The below is just arbitrary numbers but
the trend is same as I am looking at. I appreciate if someone can
share experiences or provide some literature that I can look at.
Dose (mg) mean AUC (ug*hr/ml)
1 100
2 200
4 500
8 250
16 250
Thanks
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What is the route of administration?
Manish Issar, Ph.D
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Looks like a classic high dose hook effect. Should be a wealth of
references
on this.
Mickey
[Assay method? - db]
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Sun,
This could be due to variability as well as anything else. Is your
AUC highly variable?
Matt.
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Several things
1) saturation of carrier/transport systems
2) induction of carrier/transport systems
3) induction of enzymes
4) analytical variables
efficiency of detection
efficiency of ionization
saturation of system components
Induction is remote but you have not given us the time course or route
are the animals the same?
LC whether MS or otherwise, has limitations in detection and with MS,
with detection and ionization, Ligand binding has limitations with
binding and enzyme amplification, stability of the readout. You may
want to eliminate these analytical possibilities first, then go back
and check the biologicals.
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