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

posted by Astea – Russia, 2015-12-11 10:39 (3030 d 15:01 ago) – Posting: # 15723
Views: 27,220

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 λz values you got with bear (when input 'NA' for the last data point) and with excel? and (3) what λz 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 λz 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 λz 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"

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