Calculation of PK parameters Cmax1, AUC0-tmax1,Tmec, OT0-12, AUC0-Tmec

[glr2010]

Dear All,

How to calculate PK parameters Cmax1, AUC0-tmax1,Tmec (Time to minimum effective concentration Range of 6-10 ug/mL within the first 60 minutes), OT0-12, AUC0-Tmec in Phoenix WinNonlin 6.4. Please suggest for following data

Subject Period Time(hr) Concen(ug/mL)
1 1 0.00 0.00
1 1 0.25 9.07
1 1 0.50 16.10
1 1 0.75 19.90
1 1 1.00 15.10
1 1 1.50 11.00
1 1 2.00 11.20
1 1 2.50 6.81
1 1 3.00 6.18
1 1 4.00 3.47
1 1 4.25 6.66
1 1 4.50 11.40
1 1 5.00 16.90
1 1 5.50 16.20
1 1 6.00 10.70
1 1 6.50 10.90
1 1 7.00 6.76
1 1 8.00 5.02
1 1 8.25 4.12
1 1 8.50 6.65
1 1 9.00 15.90
1 1 9.50 16.40
1 1 10.00 12.50
1 1 11.00 7.63
1 1 12.00 5.11
1 1 16.00 1.40
1 1 20.00 0.00
1 1 24.00 0.00
1 2 0.00 0.00
1 2 0.25 3.48
1 2 0.50 7.21
1 2 0.75 8.36
1 2 1.00 11.30
1 2 1.50 10.80
1 2 2.00 11.10
1 2 2.50 10.70
1 2 3.00 8.20
1 2 4.00 6.17
1 2 4.25 6.13
1 2 4.50 5.59
1 2 5.00 5.16
1 2 5.50 5.55
1 2 6.00 3.95
1 2 6.50 4.14
1 2 7.00 3.94
1 2 8.00 3.77
1 2 8.25 3.83
1 2 8.50 4.46
1 2 9.00 3.87
1 2 9.50 4.24
1 2 10.00 4.43
1 2 11.00 5.84
1 2 12.00 9.90
1 2 16.00 6.52
1 2 20.00 3.37
1 2 24.00 1.46
1 3 0.00 0.00
1 3 0.25 0.00
1 3 0.50 0.60
1 3 0.75 3.91
1 3 1.00 5.10
1 3 1.50 6.46
1 3 2.00 8.01
1 3 2.50 7.97
1 3 3.00 6.56
1 3 4.00 12.30
1 3 4.25 11.10
1 3 4.50 12.30
1 3 5.00 15.40
1 3 5.50 18.20
1 3 6.00 20.00
1 3 6.50 14.70
1 3 7.00 14.90
1 3 8.00 10.50
1 3 8.25 11.30
1 3 8.50 11.30
1 3 9.00 9.93
1 3 9.50 8.55
1 3 10.00 7.17
1 3 11.00 4.58
1 3 12.00 3.77
1 3 16.00 0.96
1 3 20.00 0.00
1 3 24.00 0.00
2 1 0.00 0.00
2 1 0.25 0.00
2 1 0.50 0.00
2 1 0.75 0.00
2 1 1.00 0.00
2 1 1.50 2.32
2 1 2.00 5.23
2 1 2.50 11.10
2 1 3.00 16.30
2 1 4.00 33.50
2 1 4.25 38.30
2 1 4.50 36.70
2 1 5.00 34.70
2 1 5.50 25.90
2 1 6.00 28.60
2 1 6.50 20.70
2 1 7.00 20.90
2 1 8.00 12.10
2 1 8.25 12.20
2 1 8.50 9.52
2 1 9.00 7.38
2 1 9.50 5.97
2 1 10.00 5.65
2 1 11.00 4.41
2 1 12.00 3.15
2 1 16.00 0.99
2 1 20.00 0.00
2 1 24.00 0.00
2 2 0.00 0.00
2 2 0.25 5.06
2 2 0.50 11.30
2 2 0.75 14.20
2 2 1.00 18.90
2 2 1.50 17.80
2 2 2.00 16.90
2 2 2.50 16.40
2 2 3.00 16.90
2 2 4.00 12.70
2 2 4.25 14.40
2 2 4.50 13.90
2 2 5.00 10.30
2 2 5.50 10.20
2 2 6.00 12.40
2 2 6.50 13.00
2 2 7.00 7.63
2 2 8.00 6.77
2 2 8.25 7.53
2 2 8.55 8.32
2 2 9.00 7.38
2 2 9.50 7.15
2 2 10.00 8.40
2 2 11.00 11.60
2 2 12.00 15.10
2 2 16.00 5.61
2 2 20.00 2.22
2 2 24.00 1.00
2 3 0.00 0.00
2 3 0.25 6.79
2 3 0.50 18.00
2 3 0.75 20.10
2 3 1.00 19.90
2 3 1.50 17.10
2 3 2.00 15.50
2 3 2.50 11.70
2 3 3.00 9.88
2 3 4.00 8.18
2 3 4.25 17.00
2 3 4.50 24.00
2 3 5.00 25.10
2 3 5.50 21.00
2 3 6.00 20.20
2 3 6.50 16.30
2 3 7.00 11.80
2 3 8.00 8.13
2 3 8.25 5.92
2 3 8.50 8.41
2 3 9.00 21.30
2 3 9.50 18.90
2 3 10.00 18.60
2 3 11.00 13.20
2 3 12.00 10.60
2 3 16.00 2.93
2 3 20.00 0.93
2 3 24.00 0.00

Regards,

GLR

[SimonDavis]

Hi GLR2010, If you are looking for other people to help, then it would be helpful if you posted either data files or preferably Phoenix projects and explained a bit more about your data;

e.g. it looks like the plot below, are the subjects being re-dosed every 4, 6 and 12 hours depending which period they are in?

In which case you need to set up your NCA to analyse per dose profile;

1. In NCA, there is really no such thing as Cmax1, the absolute maximimum conc within a dosing interval is Cmax. If you need it per dosing profile you will need cut the profiles into the 1st dose event.

2. Tmec :Time to minimum effective concentration Range of 6-10 ug/mL within the first 60 minutes),

is it a MEC of 6 or 10? or 10 an upper limit, I’ve attached a project example using NCA PD to give these where I put in 6 as baseline and 10 as threshold

Tonset will give you the time the conc first reached 10, but for two of the profiles that will be much later than 1 h.

Subject Period Tonset (h) 1 1 0.28 1 2 0.89 1 3 3.60 2 1 2.41 2 2 0.45 2 3 0.32

3. OT0-12, not sure what you’re asking for AUC 0 to 12?

4. AUC0-Tmec see this post regarding a similar AUC to TMax calculation using an inner join after the NCA object; https://support.certara.com/forums/topic/378-wnl-output-of-auctmax/?p=1324

In future people might be happier to help you if you’ve show some of what you’ve tried before, otheriwsee theytmight feel you’re asking them to do their whole analysis for them.

And lastly MGR if you are going to crosspost to different forums it might be nice to mention that you’ve already asked elsewhere; http://forum.bebac.at/mix_entry.php?id=16553#top16553

Simon

GLR.phxproj (382 KB)