[R-sig-dyn-mod] question about the limit of conversion rate

[Daniel Reed]

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 at umich.edu
web: www.danielreed.org



On Jun 24, 2013, at 3:35 PM, <dabing.chen at 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")
> 
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> 
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