Hi,

I am trying to simultaneously model extravascular (dermal) and IV data, using a Weibull absorption model for the dermal data, as described in Ette & Williams PMetrics book (see attached).

This is the code that I am using:

test(){

WB = 1 - exp(-(Ka*time2)**gamma)

deriv(time2=1)

deriv(Aa = - (Aa * WB))

deriv(A1 = - (Cl * C)- (Cl2 * (C - C2)) + (Aa * WB))

deriv(A2 = (Cl2 * (C - C2)))

urinecpt(A0 = (Cl * C))

C = A1 / V

C2 = A2 / V2

dosepoint(A1) # this is the dosepoint for the subjects that received IV dose

dosepoint(Aa, bioavail = (F)) # this is the dosepoint for the subjects that received dermal dose

error(CEps = 1)

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

stparm(V = tvV*exp(nV))

stparm(Cl = tvCl * exp(nCl))

stparm(V2 = tvV2)

stparm(Cl2 = tvCl2 * exp(nCl2))

stparm(Ka = tvKa*exp(nKa))

stparm(F = tvF)

stparm(gamma = tvgamma*exp(ngamma))

fixef(tvV = c(692, 6925.17, ))

fixef(tvCl = c(5138, 51384,250000 ))

fixef(tvV2 = c(19360, 193607, ))

fixef(tvCl2 = c(3785, 37857, ))

fixef(tvKa = c(0, 0.02, ))

fixef(tvF = c(0.0001, 0.01,0.2 ))

fixef(tvgamma = c(0.1,1,))

ranef(diag(nCl2, nKa, ngamma) = c(1,1,1))

ranef(block(nCl, nV) = c(1, 0.1, 1))

}

Could you tell me if this is a correct implementation of Weibull absorption model? The reason I am using deriv(time2=1) is so that the WB function is calculated continuously at the same time steps as the integrator. If I bring the time in as a covariate, the WB function would be calculated only at the time points when the observations are taken.

Thanks,

Dora