## no lambda(z), no NCA? [NCA / SHAM]

Dear Helmut,

Thank you for your messages.

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

For what purpose to take blood sample after tau? Is it worth to do so?

» We should be cautious in using

Absolutely agree.

» In steady state within τ you

So, it looks like that no lambda

» Tricky.

It is inevitable for us in Taiwan or in China to conduct a multiple-dose BE/BA study when the target product is modified release dosage form.

» Accumulation index is easy – and actually the most interesting metric if we compare SD with MD. I only use

\(R=\frac{AUC_{0-\tau}}{AUC_{0-\infty}}\; \begin{matrix}

\text{(steady state)}\\

\text{(single dose)}

\end{matrix}\)

The formula is only for when conducting both a SD and a MD BE/BA studies simultaneously. If we just have a MD BE study, we still need a lambda

» V

Indeed. We calculate V

» That’s rubbish. WinNonlin uses

\(\small{R=}\frac{1}{\left| 1-\text{e}^{-\lambda_z\cdot \tau} \right|}\)

» which needs λ

Good point!

Since we're about to release next version (v2.3.3) of

Thank you for your messages.

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

For what purpose to take blood sample after tau? Is it worth to do so?

» We should be cautious in using

*‘terminal phase’*– especially in NCA. Personally I prefer*‘apparent elimination’*[...]Absolutely agree.

» 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 [...]So, it looks like that no lambda

_{z}, no NCA...» Tricky.

*I*would not try to play around with elimination from steady state*within*τ.It is inevitable for us in Taiwan or in China to conduct a multiple-dose BE/BA study when the target product is modified release dosage form.

» Accumulation index is easy – and actually the most interesting metric if we compare SD with MD. I only use

\(R=\frac{AUC_{0-\tau}}{AUC_{0-\infty}}\; \begin{matrix}

\text{(steady state)}\\

\text{(single dose)}

\end{matrix}\)

The formula is only for when conducting both a SD and a MD BE/BA studies simultaneously. If we just have a MD BE study, we still need a lambda

_{z}.» V

_{ss}is a strange metric. It sounds so easy to divide [...]Indeed. We calculate V

_{ss}just because WinNonlin does so. Not a necessary procedure in a BE study.» That’s rubbish. WinNonlin uses

\(\small{R=}\frac{1}{\left| 1-\text{e}^{-\lambda_z\cdot \tau} \right|}\)

» which needs λ

_{z}, a constant τ (what about a dose regimen of 6/6/12 or actual sampling times?), and is only valid for a one-compartmental model (the most serious drawback). [...]Good point!

Since we're about to release next version (v2.3.3) of

*, we added data analysis for MD BE/BA since this release. I used to estimate lambda***bear**_{z}of MD study with the same method that we did in SD study. However, I was not very comfortable to do so for a long time.—

All the best,

-- Yung-jin Lee

Kaohsiung, Taiwan https://www.pkpd168.com/bear

Download link (updated) -> here

All the best,

-- Yung-jin Lee

**bear v2.9.0**:- created by Hsin-ya Lee & Yung-jin LeeKaohsiung, Taiwan https://www.pkpd168.com/bear

Download link (updated) -> here

### Complete thread:

- half-life in multiple-dosed steady-state BE/BA study? yjlee168 2009-07-14 14:16 [NCA / SHAM]
- half-life in steady state; WinNonlin Helmut 2009-07-15 15:09
- no lambda(z), no NCA?yjlee168 2009-07-16 11:53
- NCA without lambda(z) Helmut 2009-07-16 14:06
- No rule is the rule - lambda(z) of MD BE yjlee168 2009-07-16 22:17

- NCA without lambda(z) Helmut 2009-07-16 14:06
- Distinguish accumulation oksanachlebko 2018-01-05 00:10

- no lambda(z), no NCA?yjlee168 2009-07-16 11:53

- half-life in steady state; WinNonlin Helmut 2009-07-15 15:09