PK PD modeling for covalent inhibitor

I was developing a PK-PD model for epigenetic covalanet inhibitor and received the following error message upon execution:

“could not merge sort times. some data that is expected to be numeric is not. please check your source data”.

Pheonix file, including mouse PK and biomarker PD data, is attached.

  1. PK model: one compartment used, though two compartment better described the PK profile.

just want to test the model first

  1. PD model: bacterial kiling DRECKER function used, with PD lag time as 8 h.

As the model can’t be executed, just wonder whether the code is correct, or not. Please advice.

Regards,

Jennifer

Dear Jennifer. I do not see attached the project. please attach it and I will help you.

best

Serge

File attached and thanks for your prompt response, Serge.

Jennifer

Yang_covalent_Inhibitor.phxproj (673 KB)

code for the model:

test(){
deriv(Aa = - Ka * Aa)
deriv(A1 = Ka * Aa - Ke * A1)
deriv(R = Kin - KoutR - KirrCR)
dosepoint(Aa, tlag = Tlag)
C = A1 / V
R0 = 132
Kin = R0
Kout
sequence{R = R0}
error(RRps = 1)
observe(RObs = R + RRps)
stparm(Kin = tvKin)
stparm(Kout = tvKout)
stparm(Kirr = tvKirr)
fixef(Ka(freeze) = c(, 1.5, ))
fixef(V(freeze) = c(, 0.005, ))
fixef(Ke(freeze) = c(, 30, ))
fixef(Tlag(freeze) = c(, 8, ))
fixef(tvKin = c(, 0.2, ))
fixef(tvKout = c(, 0.01, ))
fixef(tvKirr = c(, -0.002, ))
}

mouse PK data:

time (h) plasma conc (nM)

0 0
0.5 506
1 211
2 83.7
4 37
8 8.2
24 0.7

Biomarker Data

time(h) CD86(pg/mL)
0 117
0.5 119
1 132
2 116
4 126
8 77
24 27
48 47
72 65
96 103