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Dear all,
I have a query:
1. How is AUC calculated for an IV infusion, which is stopped say at
24 hours?
2. The back extrapolation leads us to the original extrapolated
concentration at time 0, so is that conc used to calculate kel?
Cordially,
Gupta
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The following message was posted to: PharmPK
Dear Gupta
Not sure whether AUC is calculated for infusion data. For back
extrapolation, the original y-axis is shifted to the time
corresponding to start of drug decline. If the infusion assumes 2
compartment model, then the intercepts have to be corrected.
Nadeem Irfan Bukhari
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Hi Gupta,
If you are thinking of estimating the AUC as C0/kel, you should think
again. That formula is valid when you give a bolus dose and the drug
concentrations follow a mono-exponential decay (1-compartment model).
In your case, use a trapezoidal method for the estimation.
Toufigh
Toufigh Gordi, PhD
Clinical Pharmacology, PK/PD analysis consultant
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Hi,
So do you mean that trapezoidal method on a linear graph paper would
do. But, for the first part of AUC, the C0 value (extrapolated time
zero value) will be needed. So, in case the infusion was stopped at 24
hrs, the extrapolation goes to y axis for time zero value, and that Cp
value be used in AUC?
Cordially,
Gupta
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The following message was posted to: PharmPK
Hi Gupta,
I am not sure if I understand your question well. In general, when you
give an infusion, drug concentrations start to increase from zero (at
time zero) to some level, depending on the infusion rate. If the
infusion rate is 4-5 times longer than the elimination half-life of
the drug, steady state is reached. Once you stop the infusion,
concentrations decline. As I wrote before, you can use the trapezoidal
method to estimate the AUC from time zero to your last detectable
concentration (AUC0-t). You may also estimate the total AUC (AUC0-
infinity) by estimating the AUCt-infinity using the formula Ct/kel,
where Ct is the last observed concentration and kel is the elimination
rate constant of your drug. Adding the AUCt-infinity to the AUC0-t
gives you the total AUC.
Another possible way, if you reach steady state during the 24 hrs
infusion, would be estimate the CL (CL=R0/Css, where R0 is your
infusion rate and Css is the steady state concentration), then use the
CL to get AUC (AUC=Dose/CL). However, why would you be interested in
AUC if you already know the CL?
Toufigh
Toufigh Gordi, PhD
Clinical Pharmacology, PK/PD analysis consultant
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