half-life in steady state; WinNonlin [NCA / SHAM]

posted by Helmut Homepage – Vienna, Austria, 2009-07-15 15:09  – Posting: # 3955
Views: 10,127

Dear Hsin-ya & Yung-ji!

» I just like to know if it is reasonable to estimate lambdaz when doing data analysis of a multiple-dosed steady-state (SS) BE/BA study.

Good question!

» It is because we just collect the plasma/blood sample within one dosing interval (Tau) at steady-state in a multiple-dosed BE/BA study.

Most people would do so – although I’ve seen others who took samples after τ.

» It looks like there is no such terminal phase at all in multiple-dosed BE/BA study.

We should be cautious in using ‘terminal phase’ – especially in NCA. Personally I prefer ‘apparent elimination’ or the like to express that I’m not dealing with a particular PK model.

» If it is not reasonable,…

In steady state within τ you may get a value similar to SD, but with noisy data – and if more than one compartment is needed to describe the PK – most likely not. Think about a two-compartment model with accumulation due to the ‘deep’ compartment. In SD you would only catch the first one (you think it’s elimination, but in ‘reality’ it’s only distribution). In steady state the second one becomes visible.

» … is there any way to estimate the elimination rate constant (kel), half-life, Vss or the accumulation index?

Tricky.
» In WinNonlin v5.x, lambdaz still needs to be estimated first for further calculations of other NCA parameters.

That’s rubbish. WinNonlin uses

        1
R = ────────────
    |1 – ℯ –λz × τ|


which needsAt least Phoenix/WinNonlin 6 is more flexible in dealing with irregular dose regimens and sampling times, but still uses the same method for the calculation of R. In my studies I compare AUCs from SD to MD only.

Cheers,
Helmut Schütz
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