Accumulation ratio after multiple dosing

Phoenix Certara Forums Phoenix WNL basics
1

Hi all,

I have a question about the calculation of accumulation ratio after multiple dosing in NCA.

If the study drug was given daily from Day 1 to 10 and the PK samples were collected on Day 1 and Day 10, I got two lambda_z from both Day 1 and Day 10. It looks like that the WinNonlin uses the lambda-z on Day 10 to calculate the accumulation ratio after multiple dosing: R=1/(1-e-lambda_z*24).

My question is which lambda_z should be used for the accumulation ratio calculation? Any input is appreciated!

Thank you!

LLLi

2

Hi LLLi, the accumulation ratio formula used by WNL is because sometimes only the steady state profile is processed in NCA so there is no easy way for it to calculate the actual accumulation seen.

if you do have data from the single dose day and the steady state day then you can very easily merge the results from these different days together (so they are on the same row in the work sheet) and then calculate e..g. AUCtauSS/AUCtau_D1 in a data wizard.

this was discussed some time ago;

https://support.certara.com/forums/topic/34-how-to-calculate-ratios-between-parameters-egauc/?hl=ratio

Simon.

3

Hi LLLi,

regarding accumulation ratio I highly recommend to study the following topic thoroughly:

http://forum.bebac.at/mix_entry.php?id=3954

Mittyright