how to get steady state parameters

Dear Users,
Could you please let me know how can I get steady state parameters?
For instance, I got the PK model (see below for example).
Then I did simulation, for example: once a day for 10 days at dose of 2mg.
How do I determine when PK reached the steady state? by eyballing the PK curve?
How to determine steady state AUC, Tmax, clerance, T-half, Css, Cmin and Cmax?
Many thanks

test(){
deriv(Aa = - Ka * Aa)
deriv(A1 = Ka * Aa - Cl * C)
dosepoint(Aa)
C = A1 / V

stparm(Ka = tvKa)
stparm(V = tvV)
stparm(Cl = tvCl)
fixef(tvKa(freeze) = c(, 0.22, ))
fixef(tvV(freeze) = c(, 35487, ))
fixef(tvCl(freeze) = c(, 7643, ))

Hi YongCertara,

I assume you have a good education in pharmacokinetics.

We know that according to the theory of pharmacokinetics, you can never reach steady state!

You can only approach steady state infinitely.

You need to specify your own criteria to claim that the drug has reached a near steady state. For example, the standard is: 75% of the steady state, 87.5%, 93.75%, 96.9%, 98.4%, 99.2%, 99.8%, 99.9%, 99.99%, 99.99%.

“How to determine steady state AUC, Tmax, clerance, T-half, Css, Cmin and Cmax?”

When you get a model of the drug, you can easily calculate these parameters manually.

Of course, you can also synchronize these calculations in your PML.

I think learning the “SS” of “ML Model” will help you a lot.

https://onlinehelp.certara.com/phoenix/8.3/index.html#t=topics%2FMore_on_Steady_State.htm%23XREF_56496_More_on_Steady

Sincerely,

f_yc

IF you use the set WNL to choose model 3 (1com extravascular) then you will see some of these are automatically written for you as Secondary parameters.

Typicallyu I would say SS is ‘close enough’ to being achieved between 5-7 half-lives (97-99%)

Simon.

Hi Simon,

Thank you very much

Hi,

I have attached a project file with your estimates. Also, you could find the code to calculate the parameters.

test(){
deriv(Aa = - Ka * Aa)
deriv(A1 = Ka * Aa - Cl * C)

deriv(AUCinf=C) #AUC Calculation
Tmax=peak(Cmax=C) #Tmax/Cmax Calculation
Tmin=peak(Cmin=C,min=(t >30)) #Cmin Calculation
thalf = log(2) * tvV / tvCl #Halflife

dosepoint(Aa)
C = A1 / V

error(CEps = 1)
observe(CObs = C + CEps)

stparm(Ka = tvKa)
stparm(V = tvV)
stparm(Cl = tvCl)

fixef(tvKa(freeze) = c(, 0.22, ))
fixef(tvV(freeze) = c(, 35487, ))
fixef(tvCl(freeze) = c(, 7643, ))
}

Please check on “Run Options,” to call the secondary parameters and the results will be in Results (Tab)>> Table01.

Thanks
Mouli
Forum_Simulation.phxproj (465 KB)