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PKBR
Junior

Brazil,
2019-01-25 18:27

Posting: # 19809
Views: 381
 

 Phoenix Winnonlin [Software]

Dear all,

I just have quick questions for you all - quite basic.
  • When we do NCA we have obs and pred parameters. Which is better to use? Ex: AUCobs or AUCpred?

  • When we do plasma and microdialysate experiments, but the time collections are not the same, for example, plasma collections was performed until 9 hr and microdialysis collections in tissue until 8.5 hr. Is it possible to compare the MRT in this case with different time of experiment? What about AUC? For AUC would be possible to extrapolate the concentration up to 9hr considering the k?

  • When we calculate t1/2 and MRT after iv bolus dosing and these values are different, which could be the reasons if the k is not statistically different?

Many thanks,
PKBR.

-
mittyri
Senior

Russia,
2019-01-26 22:42
(edited by mittyri on 2019-01-27 09:52)

@ PKBR
Posting: # 19810
Views: 301
 

 AUCinf, MRT, Partial AUC

Dear PKBR,


» When we do NCA we have obs and pred parameters. Which is better to use? Ex: AUCobs or AUCpred?
No one else but Helmut answered that question here

» When we do plasma and microdialysate experiments, but the time collections are not the same, for example, plasma collections was performed until 9 hr and microdialysis collections in tissue until 8.5 hr. Is it possible to compare the MRT in this case with different time of experiment?
MRT is derived from AUC and AUMC.
In WNL wordings
MRTlast = AUMClast/AUClast (bolus case)
If the coverage of PK profile is enough, the estimation of MRT would be fair enough too.

» What about AUC? For AUC would be possible to extrapolate the concentration up to 9hr considering the k?
look at the partial AUC calculation rules in WNL guide cited here. I think it is what are you looking for.

» When we calculate t1/2 and MRT after iv bolus dosing and these values are different, which could be the reasons if the k is not statistically different?
The result of statistical test depends on the assumption of distribution of parameter.
Thus since HL = ln(2)/kel
the distribution of parameters won't be the same.
Simple example in R

> t.test(1:10, y = c(7:20)) 

   Welch Two Sample t-test

data:  1:10 and c(7:20)
t = -5.4349, df = 21.982, p-value = 1.855e-05
alternative hypothesis: true difference in means is not equal to 0
95 percent confidence interval:
 -11.052802  -4.947198
sample estimates:
mean of x mean of y
      5.5      13.5

> t.test(log(2)/1:10, y = c(log(2)/7:20)) 

   Welch Two Sample t-test

data:  log(2)/1:10 and c(log(2)/7:20)
t = 2.3964, df = 9.1376, p-value = 0.03974
alternative hypothesis: true difference in means is not equal to 0
95 percent confidence interval:
 0.008506605 0.283884254
sample estimates:
 mean of x  mean of y
0.20302061 0.05682518

Kind regards,
Mittyri
PKBR
Junior

Brazil,
2019-01-28 18:54

@ mittyri
Posting: # 19818
Views: 221
 

 AUCinf, MRT, Partial AUC

Thanks!
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