Add duration of patch application in Transdermal Modelling

Phoenix Certara Forums Modelling and Simulation
1

Hello All,

Iam trying to develop Donepezil, TDS patch modelling,

When i input dose (actual dose is 175mg/50cm2 area) as 175mg at T=0 then data is fitting well, but the issue is how do I provide the input that patch was applied for 72hr duration post that patch was removed in naive pooled modelling

also what should i write in the above PML code, if i want to simulate the 175mg/50cm2 patch applied for 24 hr duration instead of 72hr, how should i do it?

i have developed the below PML code

test(){
deriv(A1 = - (VMax * C3 / (C3 + Km)) + (K23 * C2))
urinecpt(A0 = (VMax * C3 / (C3 + Km)))
deriv(Aa2 = - (Aa2 * K12))
deriv(A2 = (Aa2 * K12)- (K23 * C2))
C3 = A1 / V3
error(CEps = 1)
observe(CObs = C3 + CEps * sqrt(1 + (C3)^2 * (CMultStdev/sigma())^2))
dosepoint(Aa2, tlag = (Tlag), idosevar = Aa2Dose, infdosevar = Aa2InfDose, infratevar = Aa2InfRate)
C2 = A2 / V2
stparm(V3 = tvV3)
stparm(VMax = tvVMax)
stparm(Km = tvKm)
stparm(V2 = tvV2)
stparm(K12 = tvK12)
stparm(K23 = tvK23)
stparm(Tlag = tvTlag)
stparm(CMultStdev = tvCMultStdev)
fixef(tvV3 = c(, 141111, ))
fixef(tvVMax = c(, 1760000, ))
fixef(tvKm = c(, 24, ))
fixef(tvV2 = c(, 141, ))
fixef(tvK12 = c(, 0.027, ))
fixef(tvK23 = c(, 1.9, ))
fixef(tvTlag = c(, 4, ))
fixef(tvCMultStdev = c(, 1, ))
}

Attaching data for help

It will be of great help if any one can help

Regards
Harish

lit data.xls (25.5 KB)

2

you can specify the patch duration in your dataset or as a modeled duration it depends what you want to do and how

here is when you let it be read from the data

you will also need to take into account the speed (rate) as patches are saturated and will not deliver all the dose

3

Sorry Smoukassi,

Couldnt understand what you imply, i wanted to first fit the data obtained after 72hr patch application and then using the estimates simulate the data after 24hr patch application (let the rate of delivery of drug from the patch be same)

It would be helpful, if you could help further

Regards

Harish

4

Hi Harish,

I cannot solve your problem because I don’t know all the details

see the attached and then you let me know what you need

durationpatch.phxproj (1.27 MB)

5

Hello Smoukassi,

Thanks for sharing the project,

objective was the data which i shared earlier was obtained after 72hr patch application and the model code was shared earlier

post fitting the data with code, wanted to simulate the 24 hr patch data (decreasing the duration of patch application from 72hr to 24 hr and see how the data looks like)

Hope its clear now

Regards

Harish

6

see how I did that in the project you need to tell the software the total amount of dose delivered within the 24 hours and then if it is the same rate total dose delivered will be 1/3 of the dose delivered in 72 h

did you open the project and saw the sims for 72 and 24 h ?