NCA calculation for complexe infusion administrations

Phoenix Certara Forums Phoenix WNL basics
1

Hi,

I have to calculate PK parameters for a TK study.

The administration schedule for each animal is:

  • at 0 min a bolus (infusion 1 min) (dose: 125 mg/kg)
    • at 1 min a 1 h infusion (dose: 1125 mg/kg)
    • at 1 h a 6 h infusion (dose: 750 mg/kg)

Using NCA with dose option = IV infusion and specifying the 3 infusions.

For the CL_obs calculation and the MRT calculation, Phoenix uses only the last infusion => dose f 750 mg/kg and infusion length of 6 h

=> bad calculation of CL_obs and MRT, so VSS…

What is wrong ?

Thanks in advance

Nathalie

2

Hi Nathalie - that’s quite easy - NCA is designed to support analysis of a drug concentration profile after a single dose event. If you supply 3 doses it will calcuate from the last dose.

If you want an approximation of CL etc. from all these doses then you’ll need to combine them to one dose event ie. 0-6h and work out the average rate for that whole period. Or you could use a Compartmental model.

Simon.

(Lastly I suppose you could analyse each dose profile separately if you want bu I think with your infusion times that too woudl be fairly meaningless).

3

Thanks Simon,

I used data wizard to calculate Clp and MRT, I will probably try a compartmental model.

Nathalie