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RegisterDifferent ka and f? [Power / Sample Size]
Dear Helmut,
Different f but ratio of AUC ~ 1 with the same elimination
.
This seems to me like the discovery of a new fundamental law in pharmacokinetics
or the other way round like a violation of fundamental pharmacokinetic relationships.
AFAIK is the one-compartiment AUC formula
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.
BTW1: Your data are from f=1 for both curves as a recalculation via the Bateman function easily shows (R code):
BTW2: c0 is an educated guess. A non-linear fit gives slight different values for both curves.
BTW3: This doesn't invalidate your demonstration of different ratios for the different PK metrics, of course.
❝ Example (one-compartment, no lag time, ka 0.6 h-1 (R) and 3.905 h-1 (T), f 1 (R) and 0.85552 (T); linear trapezoidal rule for simplicity):
❝ ...
❝ ...................... T/R
❝ ——————————————————————————————————
❝ AUCt 748.96 762.32 101.78%
❝ AUC∞ 839.85 839.93 100.01%
❝ ...
❝ Kel 0.10 0.10 ← identical elimination
Different f but ratio of AUC ~ 1 with the same elimination
.This seems to me like the discovery of a new fundamental law in pharmacokinetics
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.
BTW1: Your data are from f=1 for both curves as a recalculation via the Bateman function easily shows (R code):
ct <- function(time,f,c0,ka,ke){ f*c0*(ka/(ka-ke))*(exp(-ke*time)-exp(-ka*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)
round(ct(time, f=1, c0=83.35, ka=0.6, ke=0.1),2)
round(ct(time, f=1, c0=83.35, ka=3.905, ke=0.1),2)BTW2: c0 is an educated guess. A non-linear fit gives slight different values for both curves.
BTW3: This doesn't invalidate your demonstration of different ratios for the different PK metrics, of course.
—
Regards,
Detlew
Regards,
Detlew
Complete thread:
- Fasting vs Fed study sam 2012-11-26 09:49 [Power / Sample Size]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- 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
- R code gem d_labes 2012-11-28 16:23
- Sorry. Forget it. Helmut 2012-11-28 15:42
- Different ka and f sam 2012-11-28 12:38
- Different ka and f jag009 2012-11-29 16:30
- Different ka and f?d_labes 2012-11-28 12:10
- Prasugrel jag009 2012-11-28 22:31
- Prasugrel sam 2012-11-29 04:57
- Prasugrel lukamar 2012-11-26 15:13
- 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
- For EU submission of Prasugrel venkata krishna 2013-02-23 06:40
- Prasugrel Helmut 2012-11-26 13:48
Ing. Helmut Schütz