Bioequivalence and Bioavailability Forum • Sorry. Forget it.

Sorry. Forget it. [Power / Sample Size]

posted by Helmut – Vienna, Austria, 2012-11-28 16:42 (4547 d 09:09 ago) – Posting: # 9617
Views: 16,738

Dear Detlew!

❝ This seems to me like the discovery of a new fundamental law in pharmacokinetics :cool: or the other way round like a violation of fundamental pharmacokinetic relationships.

❝

❝ AFAIK is the one-compartiment AUC formula

❝ AUCpo = f*C0/kel with C0=D/V

❝ where D is the dose, V the volume of the central compartment. If kel, D and V are the same you can't get the same AUC if your f = fraction absorbed is different.

Ouch, that hurts! Made a quick-shot yesterday – which is not a one-compartment model (in hybrid constant parameterisation), but not even a PK model at all… :no:

Try:

Ct <- function(time, f, A, alpha, beta){ f*A*(exp(-beta*time)-exp(-alpha*time)) }

time <- c(0.0, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, 16, 24)

R <- round(Ct(time, f=1,       A=100, alpha=0.6,   beta=0.1), 2)

T <- round(Ct(time, f=0.85552, A=100, alpha=3.905, beta=0.1), 2)

plot(time, R, type="b", xlim=c(0, 24), ylim=c(0, max(R, T)), ylab="conc.", axes=F)

points(time, T, type="b")

axis(side=1, at=seq(0, 24, by=4))

axis(side=2, at=seq(0, max(R,T), by=10))

box()

AUCt.pct <- round(100*(0.5*sum(diff(time)*(T[-1]+T[-length(T)]))) /

                      (0.5*sum(diff(time)*(R[-1]+R[-length(R)]))), 2)

Cmax.pct <- round(100*max(T)/max(R), 2)

cat("AUCt (T/R):", AUCt.pct, "%\nCmax (T/R):", Cmax.pct, "%\n")

The devil is in the details (the “A”). THX. Sorry. Shouldn’t forget to take my pills.

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

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Complete thread:

Fasting vs Fed study sam 2012-11-26 09:49 [Power / Sample Size]
- Prasugrel Helmut 2012-11-26 13:48
  - Prasugrel lukamar 2012-11-26 15:13
    - Prasugrel Helmut 2012-11-26 15:30
  - Prasugrel sam 2012-11-27 12:52
    - Prasugrel Dr_Dan 2012-11-27 14:19
    - Different ka and f Helmut 2012-11-27 14:56
      - Different ka and f? d_labes 2012-11-28 12:10
        
        Sorry. Forget it.Helmut 2012-11-28 15:42
        
        R code gem d_labes 2012-11-28 16:23
        
        R code gem Helmut 2012-11-28 16:54
      - Different ka and f sam 2012-11-28 12:38
        
        Different ka and f jag009 2012-11-29 16:30
    - Prasugrel jag009 2012-11-28 22:31
      - Prasugrel sam 2012-11-29 04:57
- Fasting vs Fed study drgunasakaran1 2012-11-27 14:17
  - For EU submission of Prasugrel venkata krishna 2013-02-23 06:40
    - EU: parent Helmut 2013-02-23 12:07