I am trying to optimize dosage of AMX against E.coli in animals. I followed these steps:
1- I analyzed the concentration-time data of AMX after IV and oral dosing and I found the best fit with two compartment model.
2- I generated a meta -population of 1000 drug disposition curves by MCS with different dosing regimen from 72 to 96 h post administration (steady state), with a step of 0.25 h.
3- I took PRED concentration table to NCA to compute the T>MIC.
4- The PKPD index for AMX vs. E.coli is 57% corresponding to 14h. It means that the concentration of AMX should be at least 14 h over MIC (8mg/l) during dosing interval (24h) at steady state in 90% of animals.
5- I took the data from NCA to phoenix statistical tool to find the 90% percentile (PTA).
The problem is:
The actual time interval is from 72 to 96 h, which is 24 h. but NCA gives me results of 0 to 96h.
Time high 18
Time between 55
Time low 23
This is not correct because I simulated the interval of 72-96 and the total mean values of time over MIC should be 24h, not 96h.
Do you know what should I do to deal with the issue?
P.S, please note that it is not possible to administer AMX as BID or TID in livestock.