## Washout based on mean ± SD of t½ [Design Issues]

Hi Imph

I don't know about "every" PK parameter, but FDA use this approach to plan partial AUC as well.

For example, for methylphenidate HCl ER tablet, among other parameters, FDA requests partial AUC

> "

This is the same as what Helmut did for t

Well, Tmax is discrete so it is not normal distribution either. FDA still use it for the approximation for pAUC.

I'd use this 5 x (mean(PK) + 2xSD(PK)) instead of the empirical "7 x mean(PK)".

❝ I would like to know if this method can be applied to each pharmacokinetic measurement, for example to determine the duration of the sampling (5 x t1/2) or to calculate the predose limit of 5% Cmax when the Cmax is provided in the literature under mean+/-SD.

I don't know about "every" PK parameter, but FDA use this approach to plan partial AUC as well.

For example, for methylphenidate HCl ER tablet, among other parameters, FDA requests partial AUC

_{0--3h}and AUC_{0--4h}for fasting and fed studies, respectively. The reason was that the Tmax was 2h under fasting and 3h under fed. the standard deviation (SD) of Tmax is about 0.5h, so 2 x SD is 1h, according to FDA:> "

*For Tmax, two standard deviations = 1.0; Generally, approximately 95% of observations fall within two standard deviations of the mean; Thus, since the Tmax from the immediate-release portion of this formulation is about 2 hours under fasting conditions and 3 hours under fed conditions, pAUCs calculated to 0-3 hours in a fasting BE study and 0-4 hours in a fed BE study should capture the responses of 95% of the subjects. This should provide assurance that a test and reference product will be therapeutically equivalent over the early part of the daily dosing interval, corresponding to onset of response.*" (see ref linked here)This is the same as what Helmut did for t

_{1/2}in his PPT cited in previous post.❝ In the reference you gave, a normal distribution is assumed, but pharmacokinetic measurements do not generally follow a normal distribution but a log-normal one. Does this method still apply?

Well, Tmax is discrete so it is not normal distribution either. FDA still use it for the approximation for pAUC.

I'd use this 5 x (mean(PK) + 2xSD(PK)) instead of the empirical "7 x mean(PK)".

—

All the best,

Shuanghe

All the best,

Shuanghe

### Complete thread:

- Washout based on mean ± SD of t½ Imph 2022-09-25 13:52 [Design Issues]
- Washout based on mean ± SD of t½ Helmut 2022-09-25 16:08
- Washout based on mean ± SD of t½ Imph 2022-09-26 15:24
- Washout based on mean ± SD of t½Shuanghe 2022-09-26 17:34
- Washout based on mean ± SD of t½ Helmut 2022-09-26 17:35
- If you have data… Helmut 2022-09-27 11:52
- If you have data… Imph 2022-10-25 09:21

- Washout based on mean ± SD of t½ Imph 2023-05-26 23:31
- Washout based on mean ± SD of t½ Helmut 2023-05-27 06:52
- Washout based on mean ± SD of t½ Imph 2023-05-27 08:36

- Washout based on mean ± SD of t½ Helmut 2023-05-27 06:52

- Washout based on mean ± SD of t½ Imph 2022-09-26 15:24

- Washout based on mean ± SD of t½ Helmut 2022-09-25 16:08