Bioequivalence and Bioavailability Forum

Eyeball-PK [NCA / SHAM]

posted by Helmut  – Vienna, Austria, 2012-07-11 16:37 (4663 d 19:14 ago) – Posting: # 8931
Views: 24,205

Dear Hiren!

❝ ❝ ❝ ❝ ❝ ❝ […] Once the infusion is over pharmacologically the only phase running in human body is elimination of drug as absorption is completed (end of infusion).

There is no absorption if the drug is administered directly to the central compartment. In rare cases you may notice an increase of concentrations after the end of infusion. This may occur if the drug precipitates in the vein. Then you have a true absorption process (actually dissolution). Dissolution may take place either in the vein itself or (downstream) in the lungs.

❝ ❝ Please avoid SMS spelling in your messages on this forum.

❝ sorry as I am new to this forum

… still a newbie after >2½ years?

❝ Then how can you assume monophasic when calculating Kel for extra vascular drug administration. May be when you are calculating Kel for a tablet distribution is still on??

For monophasic PK see footnote 1 of this post. Note that the TTT-method was developed for monophasic PK only – justified by irrelevant absorption after the inflection point of the profile. For multiphasic profiles the authors suggest as the starting point the intersection of the last phase with the preceding one. This point might be difficult to find, especially if the distribution phase is not substantially faster than elimination. Any algorithm might fail here; visual inspection of the fit is mandatory (see the quotes from the TTT-paper above and from Hauschke et al. above).

❝ So I think conclusion is that manual selection coupled with statistical method is best irrespective of dosage form....

❝ Is it OK?

I would do it the other way ’round. Start with an automatic method and adjust the selected time points if deemed necessary.

❝ Now if I am using this + I know that my drug is having instantaneous distribution then still I should go for manual linearity finding. Will it not be bias???

Concentrations are not measured without error. It might be that – especially with long half lives and values close to the LLOQ – any automatic method fails. To avoid bias I suggest to perform the estimation of λ_z blinded for treatment and import the randomization afterwards. At least this is what I do.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

• Methods for calculation of half lives d_labes 2008-02-01 14:58 [NCA / SHAM] 
  • Methods for calculation of half lives Helmut 2008-02-01 16:59
    • Methods for calculation of half lives Ohlbe 2008-02-02 23:00
      • Minimum AIC?! Helmut 2008-02-03 13:49
        • G (Kinetica) = R²adj (WinNonlin) Helmut 2008-02-04 01:12
    • Methods for calculation of half lives d_labes 2008-02-04 16:43
      • MAIC and beyond... Helmut 2008-02-04 17:49
  • TTT method Helmut 2008-05-10 13:56
    • TTT method d_labes 2008-05-16 09:12
      • TTT method Helmut 2008-05-16 17:21
        • TTT method d_labes 2008-05-23 15:43
          • TTT method hiren379 2012-07-11 11:11
            • TTT method Ohlbe 2012-07-11 11:37
              • TTT method hiren379 2012-07-11 11:44
                • TTT method Ohlbe 2012-07-11 12:16
                  • TTT method hiren379 2012-07-11 12:53
                    • Eyeball-PKHelmut 2012-07-11 14:37
                      • Eyeball-PK hiren379 2012-07-11 15:28
                        • Eyeball-PK Helmut 2012-07-11 15:47
                          • Eyeball-PK hiren379 2012-07-11 16:24