PK-basics / terminology issues [Software]

posted by Helmut Homepage – Vienna, Austria, 2009-09-18 15:55 (5714 d 17:40 ago) – Posting: # 4216
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Dear Vuvraj!

❝ I have got following parameters:

❝ Tmax, Cmax, AUC, Vz_Obs, Vz_Pred, Vss_Obs, Vss_Pred, CL_Obs, CL_Pred.


You can’t learn pharmacokinetics from a webforum. I would strongly suggest to read textbooks on PK, get some training in PK, or – as a starter – have a look at David Bourne's excellent A First Course in Pharmacokinetics and Biopharmaceutics. It doesn’t make sense to click through a piece of specialized software without knowledge of the basics behind. Sorry, there are no shortcuts.

Again, RTFM! For NCA formulas see WinNonlin’s User's Guide > WinNonlin Model Libraries > Noncompartmental analysis > Plasma or serum data.

There’s no consensus on terminology in PK. This may sound strange more than 50 years after publication of the first textbook.1 That’s the reason many papers in the Journal of Pharmacokinetics and Pharmacodynamics still contain a section of abbreviations and definition of terms. ;-)

❝ [...] how to calculate Vc?

❝ Is Vc or Vz_obs same?


Vc is the Volume of the central compartment in a multi-compartment model used in textbooks e.g, Gibaldi/Perrier,2 Wagner,3 and more recently Gabrielsson/Weiner.4 WinNonlin uses the term V1 for the central and V2-3 for the first and second [sic] peripheral compartment(s). Unless your drug shows more than one segment in a semilog plot and you perform PK-modeling, you will not obtain Vc. Therefore in NCA you only get parameters based on the apparent elimination phase.

Even if Vc is used, the numbering of transfer rate constants still uses 1 for the central compartment:[2, p.49]

+-------------+  k12   +-------------+
|   Central   | ----→ | Peripheral  |
| Compartment | ←---- | Compartment |
+-------------+  k21   +-------------+
       |
       | k10
       ↓

Note: k12, k21, k10 (not kc2, k2c, kc0). The index 0 denotes ‘one-way-compartment’ of no defined volume. For extravasal administration the absorption rate constant is given as k01 (or ka), all elimination processes are denoted by ki0 (e.g., k10 from central or k20 from the first peripheral). In a one-compartment model elimination sometimes is also denoted as kel. All elimination processes may be composites of elimination of the parent drug and formation of metabolite(s). Unless you have metabolite data, you cannot distinguish between them. If multi-compartment models are concerned, there are many (!) different ones describing the data equally well (i.e., the same minimum SSQ, but different parameter values). Sampling from only the central compartment will give you no clue, which one is the “right” one. This problem is called model identifiability. You see, PK can be quite tricky. Therefore, if possible stick with NCA until you know what to do.

For PK formulas see WinNonlin’s User’s Guide > WinNonlin Model Libraries > Pharmacokinetic models >
    References:
  1. Dost FH. Der Blutspiegel: Kinetik der Konzentrationsabläufe in der Kreislaufflüssigkeit. Leipzig: Thieme-Verlag; 1953 (in German).
  2. Gibaldi M, D Perrier D. Pharmacokinetics. New York: Marcel Dekker; 2nd ed. 1982 (reprint: New York: informa healthcare; 2007).
  3. Wagner JG. Pharmacokinetics for the Pharmaceutical Scientist. Lancaster: Technomic Publishing; 1993.
  4. Gabrielsson J, Weiner D. Pharmacokinetic & Pharmacodynamic Data Analysis: Concepts and Applications. Stockholm: Swedish Pharmaceutical Press; 4th edition 2006.

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