Bioequivalence and Bioavailability Forum • if Clast is zero in bear

if Clast is zero in bear [🇷 for BE/BA]

posted by Astea – Russia, 2015-12-11 10:39 (3479 d 10:24 ago) – Posting: # 15723
Views: 29,466

Dear yjlee168!
I'm very grateful for your reply!

❝ In order to verify your results as posted, could you please tell me (1) what AUC calculation method you used with bear ('all linear' or 'linear-up/log-down')? (2) what λ_z values you got with bear (when input 'NA' for the last data point) and with excel? and (3) what λ_z calculation did you use with non-manual selection of data points? Thanks again.

1). I used linear-up/log-down method (1)
2). When 'NA' is marked for the last point BEAR gets λ_z in the following form (below I attach all the results for the verification):

<< NCA Outputs:- <Subj.# 1 > (Ref.)>>

--------------------------------------------------------

 subj  time   conc  AUC(0-t) AUMC(0-t)

    1  0.00    0.0     0.000     0.000

    1  0.25   36.1     4.513     1.128

    1  0.50  125.0    24.650    10.069

    1  0.75  567.0   111.150    71.037

    1  1.00  932.0   298.525   240.694

    1  1.50 1343.0   867.275   977.319

    1  2.00 1739.0  1637.775  2350.444

    1  3.00 1604.0  3309.275  6495.444

    1  4.00 1460.0  4841.275 11821.444

    1  8.00  797.0  9355.275 36253.444

    1 12.00  383.0 11715.275 58197.444

--------------------------------------------------------



<< Selected data points for lambda_z calculations >>

----------------------------------------------------

 subj seq prd drug time conc

    1   2   2    1    4 1460

    1   2   2    1    8  797

    1   2   2    1   12  383



  << Final PK Parameters >>

-----------------------------

           R sq. = 0.99698 

Adj. R sq. (ARS) = 0.99397 

        lambda_z = 0.16727 

            Cmax = 1739 

            Tmax = 2 

            Cl/F = 7.1403 

            Vd/F = 42.687 

         T1/2(z) = 4.1439 

        AUC(0-t) = 11715 

      AUC(0-inf) = 14005 

       AUMC(0-t) = 58197 

     AUMC(0-inf) = 99363 

        MRT(0-t) = 4.9677 

      MRT(0-inf) = 7.0948 

-----------------------------





Excel calculations:

lambda_z=0,167269591

AUClast=11715,2750

AUCinfobs=14004,9918

And when we leave "0" and choose manual selection (three points):

<< NCA Outputs:- <Subj.# 1 > (Ref.)>>

--------------------------------------------------------

 subj  time   conc  AUC(0-t) AUMC(0-t)

    1  0.00    0.0     0.000     0.000

    1  0.25   36.1     4.513     1.128

    1  0.50  125.0    24.650    10.069

    1  0.75  567.0   111.150    71.037

    1  1.00  932.0   298.525   240.694

    1  1.50 1343.0   867.275   977.319

    1  2.00 1739.0  1637.775  2350.444

    1  3.00 1604.0  3309.275  6495.444

    1  4.00 1460.0  4841.275 11821.444

    1  8.00  797.0  9355.275 36253.444

    1 12.00  383.0 11715.275 58197.444

    1 24.00    0.0 14013.275 85773.444

--------------------------------------------------------



<< Selected data points for lambda_z calculations >>

----------------------------------------------------

 Subj Time Conc

    1    4 1460

    1    8  797

    1   12  383



  << Final PK Parameters >>

-----------------------------

           R sq. = 0.99698 

Adj. R sq. (ARS) = 0.99397 

        lambda_z = 0.16708 

            Cmax = 1739 

            Tmax = 2 

            Cl/F = 7.1361 

            Vd/F = 42.71 

         T1/2(z) = 4.1485 

        AUC(0-t) = 14013 

      AUC(0-inf) = 14013 

       AUMC(0-t) = 85773 

     AUMC(0-inf) = 85773 

        MRT(0-t) = 6.1209 

      MRT(0-inf) = 6.1209 

-----------------------------



Excel calculations:

lambda_z=0,167269591

AUClast=11715,2750

AUCinfobs=14004,9918

It seems to me very strange that λ_z in BEAR are slightly different: 0.16708 and 0.16727. And the question is why the first method (that is calculating with manually selected 3 points) fails.

—
"Being in minority, even a minority of one, did not make you mad"

Complete thread:

bear v2.7.0 released yjlee168 2015-12-07 09:18
- Suggestion ElMaestro 2015-12-07 10:12
  - Suggestion yjlee168 2015-12-07 10:55
    - Suggestion Helmut 2015-12-07 14:01
      - Suggestion yjlee168 2015-12-07 18:51
- bear v2.7.0 released Astea 2015-12-10 16:36
  - if Clast is zero in bear yjlee168 2015-12-10 17:23
    - if Clast is zero in bear Astea 2015-12-10 20:50
      - if Clast is zero in bear yjlee168 2015-12-11 03:28
        
        if Clast is zero in bearAstea 2015-12-11 09:39
        
        if Clast is zero in bear yjlee168 2015-12-11 17:16
    - bear v2.7.1 yjlee168 2015-12-15 10:21
      - bear v2.7.1 Astea 2015-12-15 19:32
        
        BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-15 20:17
        
        BLLOQ ≠ 0 with measured drug plasma conc. Helmut 2015-12-16 01:45
        
        BLLOQ ≠ 0 with measured drug plasma conc. yjlee168 2015-12-16 11:38
        
        BLLOQ ≠ 0 ∀ t > 0 Helmut 2015-12-16 12:40
        
        BLLOQ ∋ { 0, ≈0, BLLOQ{...} ∀ t > 0} yjlee168 2015-12-16 18:22
        
        BLLOQ at first two time ponts, AUC calculation Astea 2016-01-30 17:11
        
        zero-zero with AUC calculation in bear yjlee168 2016-01-30 19:00
        
        BQL rules in bear mittyri 2016-02-01 22:16
        
        BQL rules in bear yjlee168 2016-02-02 10:59
        possible solutions? yjlee168 2016-02-02 21:30
        zero (0), missing (NA), or BLLOQ (0 or NA) in bear yjlee168 2016-02-03 09:04
        
        zero (0), missing (NA), or BLLOQ (0 or NA) in bear mahmoud-teaima 2016-02-08 21:28
        
        Please avoid Full Quotes (“TOFU”)! Ohlbe 2016-02-09 00:51
        
        error message in bear mahmoud-teaima 2016-02-09 04:55
        
        please check your dataset file yjlee168 2016-02-09 06:40
        
        please check your dataset file mahmoud-teaima 2016-02-09 15:00
        
        please check your dataset file yjlee168 2016-02-09 15:38
        
        A possible R bug? yjlee168 2016-02-09 19:14