Bioequivalence and Bioavailability Forum • Spaghetti & other pasta

Spaghetti & other pasta [NCA / SHAM]

posted by Helmut – Vienna, Austria, 2013-05-23 23:29 (4363 d 14:15 ago) – Posting: # 10633
Views: 19,756

Dear Yung-jin!

❝ […] From your plots, it looks like lin-up/log-down method is more close to actual AUC. In this case, it does no matter what there is any missing data or not. Lin-up/log-down is more accurate than linear, isn't?

I think so. Whatever PK a drug follows, distribution/elimination likely is first order (well, leaving :party:

and Michaelis-Menten aside).

❝ Weird indeed but very convincible. […] How do you plot the low-right graph? Is it possible to overlap both the lower-left and the lower-right graph as one plot?

Sure. Just interpolate linear within each decreasing segment. Alternatively to lines 12–17 you could set up a function and use curve(). Was too lazy.

t <- c(0,0.5,0.75,1,1.5,2,2.5,3,4,6,8,16,24)

C <- c(0,69.59,84.64,92.61,96.73,93.45,87.51,

       80.85,68.02,47.54,33.17,7.86,1.86)

plot(t, C, type="p", ylim=c(1, max(C)*1.1), log="y", las=1,

  main="semilogarithmic", cex.main=1.1,

  xlab="time", ylab="concentration")

lines(t, C, col="blue")

for (j in 1:(length(t)-1)) {

  if (C[j+1] >= C[j]) {

    lines(x=c(t[j], t[j+1]), y=c(C[j], C[j+1]), col="blue")

  } else {

    tk <- NULL; Ck <- NULL

    for (k in seq(t[j], t[j+1], length.out=10)) {

      tk <- c(tk, k)

      Ck <- c(Ck, C[j]+abs((k-t[j])/(t[j+1]-t[j]))*(C[j+1]-C[j]))

    }

    lines(tk, Ck, col="red")

  }

}

rug(t, side=1)

legend("topright",

  c("trapezoidal rules", "linear", "lin-up/log-down"),

  lty=c(NA, 1, 1), col=c(NA, "red", "blue"))

If you want to use the code in a linear plot, interpolate logarithmically, i.e., change line 15 to
Ck <- c(Ck, exp(log(C[j])+abs((k-t[j])/(t[j+1]-t[j]))*(log(C[j+1])-log(C[j]))))

❝ Me either. Why do you think that it would be a tough job for commercial software?

I have no experiences with SAS, but in Phoenix/WinNonlin it is tricky indeed.

❝ […] But I don't quite understand why you want to add rug() plot? We don't have many data points in each subject (usually less than 50's in each period) for a BE/BA study.

It was just an idea to display the sampling schedule. Forget it. ;-)

—
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Helmut Schütz

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Complete thread:

handling of missing data gracehung 2013-05-20 07:35
- Lin-up/log-down trapezoidal avoids most trouble Helmut 2013-05-20 14:22
  - Lin-up/log-down trapezoidal avoids most trouble yjlee168 2013-05-22 08:25
    - Multiple peaks: fallback to linear trapezoidal Helmut 2013-05-22 20:25
      - Multiple peaks: fallback to linear trapezoidal yjlee168 2013-05-22 21:57
        
        No interpolation Helmut 2013-05-22 23:25
        
        No interpolation yjlee168 2013-05-23 11:43
        
        Spaghetti & other pasta Helmut 2013-05-23 15:15
        
        Spaghetti & other pasta yjlee168 2013-05-23 20:47
        
        Spaghetti & other pastaHelmut 2013-05-23 21:29
        
        Spaghetti & other pasta yjlee168 2013-05-23 22:46
        
        Spaghetti & other pasta Helmut 2013-05-24 01:24
        
        Spaghetti & other pasta yjlee168 2013-05-24 09:17
        
        No interpolation Ken Peh 2013-05-30 19:55
        
        Different algos! Helmut 2013-05-30 22:38
        
        Different algos! Ken Peh 2013-06-03 17:52
        
        Calculate what? Helmut 2013-06-03 18:11
    - Lin-up/log-down trapezoidal example Helmut 2013-05-25 15:09
      - Lin-up/log-down trapezoidal example yjlee168 2013-05-25 19:45
- handling of missing data Ohlbe 2013-05-20 21:45
  - Sorry Helmut 2013-05-21 13:53
    - Sorry gracehung 2013-05-23 01:06
      - Uncertain time point Helmut 2013-05-23 01:35