Zero-order absorption 2-compartment model

Phoenix Certara Forums Modelling and Simulation
1

Hi,

I’m trying to build a 2-compartment model with zero-order absorption. Based on other posts, I started with a 2-compartment IV model, then modified it to include zero-order absorption by adding Tabs for duration. I’m not sure if the code I’m running is accurate, could you help me take a look? Thanks!

test(){
	deriv(A1 = - (Cl * C)- (Cl2 * (C - C2)))
	urinecpt(A0 = (Cl * C))
	deriv(A2 = (Cl2 * (C - C2)))
	C = A1 / V
	dosepoint(A1, duration = (Tabs), idosevar = A1Dose, infdosevar = A1InfDose, infratevar = A1InfRate)
	C2 = A2 / V2
	error(CEps = 1.12709112056895)
	observe(CObs = C * (1 + CEps), bql)
	stparm(V = tvV * exp(nV))
	stparm(Cl = tvCl  * exp(nCl))
	stparm(V2 = tvV2 * exp(nV2))
	stparm(Cl2 = tvCl2 * exp(nCl2))
	stparm(Tabs = tvTabs * exp(nTabs))
	fixef(tvV = c(, 48, ))
	fixef(tvCl = c(, 20, ))
	fixef(tvV2 = c(, 20, ))
	fixef(tvCl2 = c(, 3, ))
	fixef(tvTabs = c(, 1, ))
	ranef(diag(nCl, nV2, nV, nCl2, nTabs) = c(1, 1, 1, 1, 1))
}
2

broadly speaking this looks OK to me, however I’d be cautious about the default value of initial estimates of 1 for this line

if you change omegas from 1 (high) to e.g. 0.1 (more typical value)

ranef(diag(nCl, nV2, nV, nCl2, nTabs) = c(0.1, .1,0.1, .1,0.1))

Also note that Naive pooled engine is not suited to optimize omegas so if you are still running in Individual mode they are not used and not optimized. Since they are presented in the model, NLME tries to keep it (i.e. for the case if the user decides to switch the engine and/or perform a Pop fit or Sim)

3

Hi Simon,
Thanks for the quick response! Would you mind pointing out which line is specifying the Naive Pooled engine? I’m trying to run the population model using the Laplacian engine instead. How should I change this?

Thanks again!

4

you should be fine then, the engine is specified in the run options tab, where you have already chosen Laplacian, I was just giving a general warning if you were trying to use this code in naïve pool mode.

1 Like