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Good reporting practices [NCA / SHAM]

posted by Helmut Homepage - Vienna, Austria, 2018-05-17 13:20  - Posting: # 18774
Views: 441

Hi Lakshimi,

» I would like to know about the PK parameters with respective to elimination rate constant.
»
» generally Kel will use as a secondary parameter in PK analysis.

Given your wording I guess you are talking about NCA and not PK modeling (that’s why I changed the category of your post). In the former you estimate PK metrics and in the latter PK parameters. ;-)

» one of regulatory audit (FDA) suggested that, u need to perform the Kel lower and Kel upper. Thereafter we are keeping the Kel lower and Kel upper parameter in the protocol …

Can you give the exact terms the FDA’s inspector used?
I assume that the inspector meant to report the time span you used in the estimation of λz. BTW, never ever rely on the automatic method implemented in software! Visual inspection of fits by a pharmacokineticist (with optional correction) is mandatory.1,2 In order to avoid bias, NCA should be performed blinded for treatment and the randomization linked to the results after locking the data base.

» … as well as performing the PK analysis for the both parameters.

What do you mean by that?

» […] what is the technical reason behind the Kel Lower and Kel upper.

Traceability of your estimations (making the life of assessors less miserable). Good practice3,4 for decades. You will find these references quoted in standard textbooks about BE testing. Part of the output of standard PK software (e.g., in Phoenix/WinNonlin given as Lambda_z_lower and Lambda_z_upper).
For a bad example (i.e., not giving the times) see this presentation.


  1. Hauschke D, Steinijans VW, Pigeot I. Bioequivalence Studies in Drug Development: Methods and Applications.New York: Wiley; 2007. p. 20–23.
  2. Scheerans C, Derendorf H, Kloft C. Proposal for a Standardised Identification of the Mono-Exponential Terminal Phase for Orally Administered Drugs. Biopharm Drug Dispos. 2008; 29(3): 145–57. doi:10.1002/bdd.596.
  3. Schulz H-U, Steinijans, VW. Striving for standards in bioequivalence assessment: a review. Int J Clin Pharm Ther Toxicol. 1991;29(8):293–8. PMID 1743802.
  4. Sauter R, Steinijans VW, Diletti E, Böhm E, Schulz H-U. Presentation of results from bioequivalence studies. Int J Clin Pharm Ther Toxicol. 1992;30(Suppl.1):S7–30. PMID 1601535.

Cheers,
Helmut Schütz
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