Hi Certara PK community!
I'm hoping someone has a simple answer for something that has me puzzled regarding NPS. I'm using NPS to predict PK following 10 days of once-daily dosing of 800 mg based on PK data obtained from 10 days of once-daily dosing of 400 mg. Please see profiles in attached image.
The yellow and purple curves are actual mean data obtained from Days 1 and 10 respectively), and the blue circles are Day 10 concentrations predicted from NPS.
As you will see from the inset text boxes, the only difference between the upper and lower graphs is the loading dose. The t1/2 from NCA of the observed Day 10 data ranges from 5 to 12h, so based on the usual assumptions by Day 10 we should be at steady state. On this basis the loading should have no effect on the Day 10 predicted profile, so I am confused as to why we see such a difference between the two graphs above, particularly when a 400 mg loading dose results in what looks like super-proportional increase in Day 10 exposure?!
Any help very gratefully received
Edited by simon.hutchings, 22 April 2021 - 03:07 PM.