PharmPK Discussion - Estimation of terminal half-life when Clast is higher

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On 26 Mar 2013 at 09:26:19, yctsai.-at-.dcb.org.tw sent the message


Dear all,

In non-compartmental analysis, terminal elimination rate constant is
obtained through linear regression of at least three time points from
the terminal phase, but occasionally we may got the terminal phase in a
"non-decline" pattern. For example, the Clast may be higher than
previous measurable concentrations. It occurs particularly when drug
concentrations close to quantifiable limit at the last several time
points. I think this is analytical related problems in determining trace
amount of the drug. But in case we don't want to put too much effort in
improving bioanalysis since it is time consuming and it isn't worth in
drug screening, I'm wondering how can we evaluate PK profiles with such
kind of data? Is it proper to just exclude these "abnormal" points? Or
using compartmental analysis instead? I appreciate anyone's comments and
suggestions.

Ralf

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On 26 Mar 2013 at 16:37:47, (Soujanya.Sunkaraneni.aaa.sunovion.com) sent the message


The following message was posted to: PharmPK

Hi Ralf,

Yes to my knowledge, those abnormal points can be excluded at your
discretion, as you know lambda_z estimation is subjective.

Thanks,
Soujanya

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On 26 Mar 2013 at 10:04:11, Walt Woltosz (walt.aaa.simulations-plus.com) sent the message


The following message was posted to: PharmPK

Ralf,

Noncompartmental analysis is a gross oversimplification in many instances.

The state-of-the-art today is to use PBPK models, or at least
compartmental models that may require multiple compartments, depending on
the drug's behavior.

Best regards,

Walt

Walt Woltosz
Chairman and CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534

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On 26 Mar 2013 at 17:10:13, (azia_karim.aaa.yahoo.com) sent the message


The following message was posted to: PharmPK
Yes you are right. WinNonLin gives you an option not to use an obviously
artifact value. You do have to give a credible reason why a particular
concentration value was not used in the regression analysis.

Aziz

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On 26 Mar 2013 at 09:27:01, Aziz Karim (azia_karim.at.yahoo.com) sent the message
```
One approach would be to use Clast (predicted) which is available in WinNonLin.

Regards.

Aziz
```
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