Bioequivalence and Bioavailability Forum

Calculation of time above MIC [🇷 for BE/BA]

posted by Helmut  – Vienna, Austria, 2008-06-29 04:24 (6144 d 01:50 ago) – Posting: # 1984
Views: 35,498

Dear Ace,

❝ Prats et al. came up with a time of 102.5 hours and 94.9% of total time in SS.

I overlooked this hint. The end of the last dosage interval therefore is 102.5/.949 = 108 hours, which is strange. I would set it to the time of the last dose plus one dosage interval (tau). If tau=12h, then the end should be set to 120h.

❝ But anyway, with your reply, I started over and finally it works!

OK, checked it again, this time with the last time point 108 hours (later samples dropped):
time <- c(0.5,1,3,5,8,12,24,36,48,60,72,84,96,108)
conc <- c(0.64,0.7,1.39,1.35,0.67,1.48,0.32,2.08,0.87,0.93,1.09,
          0.59,1.01,0.47)
dat  <- data.frame(time, conc)

f <- function(dat, th) {
  under <- 0
    for (i in which(dat$conc < th)) {
      if (!is.na(dat$conc[i-1])) {
        y <- dat$conc[c(i-1,i)]
        x <- dat$time[c(i-1,i)]
        slope <- coef(lm(y~x))[2]
        under <- under + x[2]-x[1]-(th-y[1])/slope
      }
      if (!is.na(dat$conc[i+1])) {
        y <- dat$conc[c(i,i+1)]
        x <- dat$time[c(i,i+1)]
        slope <- coef(lm(y~x))[2]
        under <- under + (th-y[1])/slope
      }
    }
  return(under)
}

th        <- 0.517
last      <- 108
occupancy <- last - f(dat, th)
coverage  <- 100*occupancy/last
cat(" End of last dosing interval:",last,"\n",
    "Occupancy time:",occupancy,"\n",
    "Coverage:",coverage,"%\n")

Now I’m getting 103.6 hours (Coverage 95.9%) in agreement with Excel and even a manual calculation.
I have no idea how the reference’s results (102.5 hours/ 94.9%) were obtained (last 120 h yields in 114.5 h / 95.4%).
The R code right now needs a little cosmetics for t=0/c=0 (returns 'error in if (!is.na(dat$conc[i - 1])) { : Argument has lenght 0') - although the result is still correct.

BTW, I looked the reference up; I’m afraid it will not be very helpful:

Skelly JP. Issues and controversies involving controlled-release drug product studies. Pharmacy International. Nov. 1986: 280–6.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• Calculation of time above MIC Aceto81 2008-06-26 16:31 
  • Calculation of time above MIC Helmut 2008-06-26 18:58
    • Calculation of time above MIC Aceto81 2008-06-26 21:50
      • Calculation of time above MIC Helmut 2008-06-27 00:18
      • Calculation of time above MICHelmut 2008-06-29 02:24
        • Calculation of time above MIC Aceto81 2008-06-30 15:50
          • Therapeutic Occupancy Time / MEC Helmut 2008-06-30 16:45
    • Time above MIC (WinNonlin 5.2.1) Helmut 2008-08-08 20:38
      • Time above MIC (WinNonlin 5.2.1) Aceto81 2008-08-12 09:56
        • Time above MIC (WinNonlin 5.2.1) Helmut 2008-08-12 12:32
          • Time above MIC (R function) Aceto81 2008-08-13 11:19
            • Time above MIC (R function) Helmut 2008-08-13 13:18
              • Time above MIC (R function) Aceto81 2008-08-13 15:35
          • Phoenix-WinNonlin 6.0 released 29 May 2009 SDavis 2009-06-04 10:55
            • Phoenix-WinNonlin 6.0 Helmut 2009-06-04 11:57
              • Phoenix-WinNonlin 6.0 - introductory webinars SDavis 2009-06-04 18:50
                • Phoenix-WinNonlin 6.0 - introductory webinars Helmut 2009-06-04 23:40
      • TimeLow Astea 2017-10-28 22:15
        • PHX/WNL 8.0 vs. previous releases Helmut 2017-10-28 23:20
          • PHX/WNL 8.0 vs. previous releases Astea 2017-10-28 23:49
        • Occupancy, Half Value Duration, Plateau Time in Phoenix/WinNonlin 8 Helmut 2017-10-30 13:18
          • Occupancy, Half Value Duration, Plateau Time in Phoenix/WinNonlin 8 Astea 2017-10-31 01:12
            • Intersections Helmut 2017-10-31 12:32
              • nobody needs it... Astea 2017-10-31 18:24