Hi Daniel:

      I increased the maxium step, I have to stop the run after 10 min. It
did not go through.

Dabing


On Mon, Jun 24, 2013 at 3:44 PM, Daniel Reed <reeddc@umich.edu> wrote:

> Hi Dabing:
>
> Have you tried increasing the maximum number of steps (i.e., maxsteps) in
> the ode() function? For example,
>
> out <- ode(y = state, t = times, func = Lorenz, parms = para, maxsteps=1e6)
>
> Cheers,
> Daniel
>
> _______________________________
> Daniel C. Reed, PhD.
> Postdoctoral Fellow,
> Dept. of Earth & Environmental Sciences,
> University of Michigan,
> Ann Arbor, MI, USA.
> email: reeddc@umich.edu
> web: www.danielreed.org
>
>
>
> On Jun 24, 2013, at 3:35 PM, <dabing.chen@boehringer-ingelheim.com> wrote:
>
> > Hi All:
> >                I am trying to simulate the rate of permeation for drug
> solution in presence of surfactant. The drug molecules can partition into
> the micelle, and the partition rate can be very fast.
> >                I wrote this code to simulation the overall permeation
> process for both free and micellized drug. I used a if function to simulate
> the below certain concentration of surfactant, the micelle will
> disintegrate, and release the incorporated drug.
> >               The problem is that I can only run it when the rate of
> partition is very low, below 0.2. When I increase the K12 to 0.6, the code
> did not run. Instead, an error message showed up like this"
> > Warning messages:
> > 1: In lsoda(y, times, func, parms, ...) :
> > an excessive amount of work (> maxsteps ) was done, but integration was
> not successful - increase maxsteps
> > 2: In lsoda(y, times, func, parms, ...) :
> >  Returning early. Results are accurate, as far as they go
> >
> >                How can I simulation at high K12?
> >                Thanks, I am looking forward for your help.
> > Dabing
> >
> >
> > rm(list=ls())
> > library (deSolve)
> >
> >
> > # permeation of micelle
> >
> > Dose <- 10 # intial dose in mg
> > SDS <- 50 # initial dose in mg
> >
> > V1 = 10 # volume of compartment A
> > V2 = 10 # volume of compartment B
> >
> >
> > # consider the reaction: 2[S]+[D] = [M]
> > # S, the monomer concentration; D, drug concentration; M, the micelle
> concentration
> >
> > state <- c(D1=Dose, M1=0,S1=SDS,T = Dose)
> >
> > para <- c(K12 <- 0.2, # partition rate from free drug to micelle drug
> >          K21 <- 0.1, # partition raet from micelle drug to free drug
> >          K1 <- 0.554/60,   # elimination rate of drug in compartment B
> >          K2 <- 1.032/60,   # elimination rate of monomer in compartment B
> >          ka1 <-  10E-4*60, # effective absorption rate constant in 1/min
> of drug A
> >          ka2 <- 9E-4*60, # effective absorption rate constant in 1/min
> of monomer
> >          Ratio <- 50) # reduction in absorption rate constant of micelle
> compared with free drug A
> >
> >
> > Lorenz <- function(t, state, para){
> > with (as.list(c(state, para)), {
> >             #set the absorpiton window, no absorption after 3 hours
> >
> >         if (S1/V1 < 0.2){
> >           K12 <- 0
> >         }else{
> >           K12 <- K12
> >         }
> >
> >
> >            dD1 <- -K12*(D1/V1)*(S1/V1)*V1 + K21*(M1/V1)*V1 -ka1*D1
> >            dS1 <- -K12*(D1/V1)*(S1/V1)*V1 + K21*(M1/V1)*V1 - ka2*S1   #
> API mass in plasma mg
> >            dM1 <-  K12*(D1/V1)*(S1/V1)*V1 -K21*(M1/V1)*V1 - ka1/Ratio*M1
>         # bile salt 1
> >            dT <-   -ka1*D1- ka1/Ratio*M1
> >
> >
> >
> > list (c(dD1, dM1,dS1,dT))
> >
> > })
> >
> > }
> >
> > times <- seq(0,300, by = 1) # simulation duration
> >
> >
> > out <- ode(y = state, t = times, func = Lorenz, parms = para)
> >
> >
> > #plot(out)
> >
> > # check dissolution mass balance
> >
> > matplot(out[,1], out[,2:5], type = "l", lwd = 3, xlab = "time (min)",
> ylab = "Mass (mg)", main="Plasma conc.ug/ml")
> > legend("right", c("free drug", "Micelle","Surfactant","Total"),pch =
> "1234",col = 1:4, text.col = 1:4,bty = "n")
> >
> >
> > matplot(out[,1], out[,c(2,3,5)], type = "l", lwd = 3, xlab = "time
> (min)", ylab = "Mass (mg)", main="Plasma conc.ug/ml")
> > legend("right", c("free drug", "Micelle","Total"),pch = "123",col = 1:3,
> text.col = 1:3,bty = "n")
> >
> >       [[alternative HTML version deleted]]
> >
> > _______________________________________________
> > R-sig-dynamic-models mailing list
> > R-sig-dynamic-models@r-project.org
> > https://stat.ethz.ch/mailman/listinfo/r-sig-dynamic-models
>
> _______________________________________________
> R-sig-dynamic-models mailing list
> R-sig-dynamic-models@r-project.org
> https://stat.ethz.ch/mailman/listinfo/r-sig-dynamic-models
>

	[[alternative HTML version deleted]]

