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Dear All:
In serial sampling pharmacokinetic Study, if concentration at 24 hr
(last sampling point) is found to be BLQ (below limit of quantification)
and if we set BLQ as zero for data analysis, then
Is AUCinf = AUC 0-24hr
Or
AUCinf = AUC 0-last + (last quantifiable concentration/k)
So there is a confusion
'what is AUCinf in this case?'
Please give your valuable suggestions
Thanks in advance
Priyadeep
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Priyadeep
First you need to be confident enough that the assay you have used is
sensitive enough to capture at least 90% of the profile. If you
analyze your data noncompartmentally using Winnonlin or any other
validated software you will automatically get the AUCinf in the
output. However, confidence on that parameter will depend on how close
your estimation of the AUCinf is compared to the AUC0-24. The
difference between the two parameters should be less than 10%, more
conservatively 5%.
If your difference between the AUC0-24 and AUCinf is greater than 10%
your assay is not sensitive enough to capture atleast 90% of the
profile hence you may have to revalidate your assay by increasing the
sensitivity of the assay.
Hope this helps.
Manish Issar, Ph.D
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Hi Priyadeep,
AUC0-inf is the total area derived for the PK model or extrapolated by
interpolation using the rate constant from the fitted regression.
AUC0-24h
in your case may be an underestimation or overestimation of the AUC0-
inf.
Regards,
Charlie
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Dear Priyadeep,
There is no confusion, what you are observing is right: if you set
C24h=0, therefore there is no extrapolation possible and you will get
AUC24=AUCinf.
In fact your last quantifiable concentration is not 24h, but the one
before that (if it's not BLQ).
Try using "missing" for your terminal BLQ values (or LOQ/2... anything
but zero)
Hope this helps,
Corinne
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Hi Priyadeep,
Since the decline in drug concentrations are normally assumed to
follow a first-order rate, theoretically there will always be some
molecules around in the body. It means that you shouldn't set the BLQ
values to 0.
I don't know how you are estimating the AUC (0-24). The AUC (0-inf)
is, as you mention below, estimated by AUC 0-last + (last quantifiable
concentration/k). I believe the AUC (0-24) can be estimated the same
way, although you will need to cut off the estimation at 24 hours time
point (most non-compartmental analysis programs can do it for you). In
any case, AUC (0-24) should be smaller than AUC (0-inf), since there
is an additional AUC (24-inf) on the top of AUC (last-24). The
difference might, of course, be very small and of no significance.
Toufigh
Toufigh Gordi, PhD
Clinical Pharmacology, PK/PD analysis consultant
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If concentration is BLQ at 24 hours it should be ignored and the AUC up
to the last measurable conc is AUClast. If you make the 24 hour sample
zero and you are using WINNONLIN for the analysis this will be AUCall, a
parameter that does not really mean anything.
AUCinfinity is AUClast plus Clast/terminal rate constant
regards
Brian
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The following message was posted to: PharmPK
I would like to make a quick comment about the response from Corinne.
If you set AUC24 concentration to zero, Auc24 will never equal AUCinf
regards
Brian
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Dear Priyadeep,
As far as my knowledge is concerned if your C24 is BLQ and you set it
to be zero for data analysis then
AUCinf = AUC0-last + (Clast/kel)
Where Clast is Concentration corresponding to Tlast.
Tlast is Time of last measurable (positive) concentration.
Kel is terminal elimination rate constant. Estimated by linear
regression of time vs. log concentration.
I would like to comment on the response from Corinne.
If you set C24 = 0 due to C24 being BLQ then AUC0-24 will never be
equal to AUCinf because Clast C24 in this case. Infact Clast is last
measurable (positive) concentration.
I hope this will help and may clear your confusion.
Thanks & Regards,
Ravi Shankar Pandey
Assistant Biostatistician
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Dear Priya Madam,
There are 2 AUC inf's . One is observed and the other one will be
predicted. I hope you are refering to AUCinf observed.
If your last time point is 24 hr and the observed cocentration at
24hr is BLQ, the Clast for the calculation of AUCinf observed will
be the preceding time point concentration. i.e. either 12th or 8th hr
concentration, depending the schedule of time points for sample
collection.
Hence, AUCinf may not be equal to AUC24 or AUClast, but some value
will be added to the AUC last.
Please correct me, if i am wrong.
Regards,
Vijender
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