obtaining elimination half life in NCA

hi Certara team,

I was trying to run an NCA to get some PK parameters including the elimination half life and the ctrough

i realized that the phoenix obtains the elimination half life (lambda z) from the slope and if the slop is positive, the phoenix will not calculate the half life unless i use the slope selector and specify the time range.

I have sampling points at steady state at predose, 2 h, 8 h , and 24 hours for about 15 patients.

when I use the time range from 0 to 24 hours i get different number as when i use 2 to 24

I am not sure why i am getting different numbers and what would be a good approach to get the half life?

also, is the ctrough (which is supposed to be just before 24 hours) the same as the clast? which is not necessarily Cmin?

thank you very much

Omamah,

Having just 4 points to descibe a curve for NCA is not very rich data and you may be better off considering analysing it as a sparse NCA.

WIthout seeing your data it’s very hard to know exactly why you get different numbers for 2-24 than 0-24 but typicallly I would not when I use the time range from 0 to 24 hours since the aim is to estimate the apparent rate of elimination and the including the conc at time zero is not likely to help this, particularly if it is extravascular dosing.

If you search for these terms in the WinNonlin user guide you will find these and other definitions

Ctrough is the conc at the end of the dosing interval e.g. just before 24 hours if once daily dosing.
Not necessairly the same as clast since this is the conc of the last quantifiable sample.

and similarly not necessarily Cmin which is the absolute minimum conc in the dosing interval, again 0-24 hours if once daily dosing.

Simon.