Metrics for absorption [NCA / SHAM]

posted by Helmut Homepage – Vienna, Austria, 2019-04-15 15:02 (1781 d 09:51 ago) – Posting: # 20167
Views: 7,155

Hi nobody,

❝ "Cmax is nonspecific to it (reflects also the extent of absorption as well as the rates of disposition processes),..."

❝ Hmm, how is AUCp not reflecting disposition processes?

It is as well. In the ideal case the sensitivity of a metric would be 1.
See Table I: Both are lousy but pAUC less so.

❝ "...lacks kinetic sensitivity even following a single administration."

❝ How much sensitivity is needed in the first place?

Duno. If we have different metrics likely it would be better to chose one with high sensitivity. I’m surprised that they didn’t explore Cmax/AUC which was shown by the two Lászlós1,2 and Lacey et al.3,4 to be superior to Cmax. Also interesting the close relationship between tmax and Cmax/AUC.5,6 My simulations are running…

❝ Or are we creating problems by "overly sensitive" methods with no relevance in clinical practice?

IMHO, the clinical relevance of the rate of absorption is doubtful. Ask a clinician about Cmax and he will tell you that is important for safety, being not aware that Emax is the trigger. Emax is linked to Cmax with a sometimes complicated function but generally dampened. If I’m interested in rapid onset I would assess tmax. But that’s another story.
Remember that current regulatory thinking concentrates on the biopharmaceutical performance of the formulation in the first place. Mentioning clinical relevance outs you as a dinosaur of BE. :-D

PS: Please don’t post in all capital letters. THX.

  1. Endrényi L, Fritsch S, Yan W. Cmax/AUC is a clearer measure than Cmax for absorption rates in investigations of bioequivalence. Int J Clin Pharmacol Ther Toxicol. 1991;29(10):394–9.
  2. Tóthfalusi L, Endrényi L. Without extrapolation, Cmax/AUC is an effective metric in investigations of bioequivalence. Pharm Res. 1995;12(6):937–42. doi:10.1023/A:1016237826520
  3. Lacey LF, Keene ON, Duquesnoy C. Evaluation of different indirect measures of rate of drug absorption in pharmacokinetic studies. 5th European Congress of Biopharmaceutics and Pharmacokinetics, Brussels, Belgium; 21 April 1993:P273.
  4. Lacey LF, Keene ON, Bye E. Evaluation of Different Metrics as Indirect Measures of Rate of Drug Absorption. In: Blume HH, Midha KK, editors. Bio-International 2. Bioavailability, Bioequivalence and Pharmacokinetic Studies. Stuttgart: medpharm; 1995. p. 73–85.
  5. Schall R, Luus HG. Comparison of absorption rates in bioequivalence studies of immediate release drug formulations. Int J Clin Pharmacol Ther Toxicol. 1992;30(5):153–9.
  6. Schall R, Luus HG, Steinijans VW, Hauschke D. Choice of characteristics and their bioequivalence ranges for the comparison of absorption rates of immediate-release drug formulations. Int J Clin Pharmacol Ther. 1994;32(7):323–8.

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