More stuff [NCA / SHAM]
another part. I love your attitudes of questioning the foundations of what we are doing. Proves that you are a true scientist.
Reach for the stars,
even if you have to stand on a cactus. Susan Longacre
❝ Capical was invented in order to explore the shape of the peak more precisely. As far as I understood it was first mentioned in an article in 19885 […] If Capical is so promising parameter, why can't I find any trials with it in results (excepting [6] and a paper on controlled release gastroretentive dosage forms tested on dogs). Or my search methods are too poor? I would be grateful if anyone will give an example of it's calculation.
That’s the first reference I’m aware of as well. Never tried it.
❝ The concentration at the end of the intended dosing interval (Cτ) should serve as an analogue of Cmin with lack of multiple dose studies.
Yes, but that’s a sad, sad story. I did my best at the GBHI in Amsterdam (2018) as well as Nuno Silva and Jack Cook in Bethesda (2019). Voices crying in the wilderness.
❝ The lag time matters when we deal with delayed-release formulations. Note that Phoenix defines it as time of observation prior to the first observation with a measurable (non-zero) concentration but not the time to the first observation with a measurable concentration. There could also be other ways7 to define it.
Correct. Lag-time means before a concentrations is measurable, hence, it cannot be the first measured one. It’s somewhere before the first measured one. As we discussed in the linked thread, I think that Detlew’s approach is pragmatic. Ref.7 would smell too much of modeling for regulators, I guess.
❝ T50%between (half-value duration)…
AFAIK, the HVD (Half Value Duration) appeared for the first time already in 19741 as \(\small{\Delta_{1/2}}\) – part of the “Retardquotient” which compares “the degree of retardation” with IR as \(\small{R_\Delta=\frac{\Delta_{1/2,MR}}{\Delta_{1/2,IR}}}\). Suggested was
\(\small{\begin{array}{ll}
R_\Delta\leqslant 1 & \text{no retardation} \\
R_\Delta\sim 1.5 & \text{weak retardation} \\
R_\Delta\sim 2 & \text{medium retardation} \\
R_\Delta\geqslant 3 & \text{strong retardation} \\
\end{array}}\)
I found it in my bible2 (stop searching; in German and out of print for ages) and some later stuff.3,4 The Two Lászlós renamed it to HaVD to avoid confusion with highly variable drugs.
Enduring the discussions about PK metrics at the GBHI-workshops was like a flash-back after a bad LSD-trip. Stirring up murky waters which cleared more than thirty years ago.
❝ "Therapeutic response" ('Where it exists, consideration must be given to the "therapeutic window."')8. But aren't there limitations that could not afford to make a statement of any correlation between plasma concentrations and effect?
You are a keen thinker! Though Jerome was head of the FDA’s CDER at that time, he felt into the trap of confusing PK with PD.
Pharmacokinetics may be simply defined as
what the body does to the drug,
as opposed to pharmacodynamics, which may be defined as
what the drug does to the body. Leslie Z. Benet
Another5 about \(\small{AUC\frac{above\, C_{av}}{below\, C_{av}}}\) (sorry, in German except the abstract):
It goes back to a proposal of the late Harold Boxenbaum6 of the days when “the flatter, the better” was a common slogan. I liked Harold because he didn’t give a shit about dress codes (always showed up in jeans, leather jacketed, wearing cowboy boots and a Stetson) and had a sharp tongue.
- Meier J, Nüesch E, Schmidt R. Pharmacokinetic criteria for the evaluation of retard formulations. Eur J Clin Pharmacol. 1974;7:429-32.
- Meier J. Bioverfügbarkeit und Absorption. In: Meier J, Rettig H, Hess H, editors. Biopharmazie. Theorie und Praxis der Pharmakokinetik. Stuttgart, New York: Georg Thieme; 1981.ISBN 3-13-603106-6. p. 247–76.
- Steinijans VW. Pharmacokinetic Characteristics of Controlled Release Products and Their Biostatistical Analysis. In: Gundert-Remy U, Möller H, editors. Oral Controlled Release Products – Therapeutic and Biopharmaceutic Assessment. Stuttgart: Wissenschaftliche Verlagsgesellschaft; 1988. p. 99–115.
- Steinijans VW, Hauschke D. Modified-Release Dosage Forms: Acceptance Criteria and Statistics for Bioequivalence. Drug Inf J. 1993; 27: 903–9. doi:10.1177/009286159302700332.
- Blume H, Siewert M, Steinijans V, Stricker H. Bioäquivalenz von per os applizierten Retard-Arzneimitteln. Konzeption der Studien und Entscheidung über Austauschbarkeit. Pharm Ind. 1989; 51(9): 1025–33.
- Boxenbaum H. Pharmacokinetic Determinants in the Design and Evaluation of Sustained-Release Dosage Forms. Pharm Res. 1984; 1(2): 82–8. doi:10.1023/A:1016355431740.
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:
- Fantastic PK parameters and where to find them Astea 2020-06-12 14:22 [NCA / SHAM]
- Fantastic post ?? Helmut 2020-06-12 16:23
- Rattleback Astea 2020-06-13 10:17
- Chatter Helmut 2020-06-13 12:28
- Reinventing the Hula-Hoop Astea 2020-06-16 01:33
- Hula-Hoop references Helmut 2020-06-16 13:07
- Prof. Keller vs. Yamaoka mittyri 2020-06-17 14:28
- SHAM(e) math Astea 2020-06-23 14:41
- SHAM(e) math Helmut 2020-06-23 15:55
- OT: Möbius strip Astea 2020-06-23 21:41
- OT: Möbius strip Helmut 2020-06-24 11:29
- OT: Möbius strip Astea 2020-06-23 21:41
- SHAM(e) math Helmut 2020-06-23 15:55
- SHAM(e) math Astea 2020-06-23 14:41
- Prof. Keller vs. Yamaoka mittyri 2020-06-17 14:28
- Hula-Hoop references Helmut 2020-06-16 13:07
- Reinventing the Hula-Hoop Astea 2020-06-16 01:33
- Chatter Helmut 2020-06-13 12:28
- Rattleback Astea 2020-06-13 10:17
- More stuffHelmut 2020-06-13 15:28
- MRT and Gravity duration mittyri 2020-06-14 22:24
- Fantastic PK parameters and where to find them ElMaestro 2020-06-16 09:46
- Cauchy distribution mittyri 2020-06-16 10:54
- Cauchy distribution Helmut 2020-06-16 13:14
- Cauchy distribution ElMaestro 2020-06-20 10:33
- noncentral normal ratio mittyri 2020-06-20 23:04
- Cauchy distribution mittyri 2020-06-16 10:54
- Fantastic post ?? Helmut 2020-06-12 16:23