martin ★★ Austria, 2011-10-18 09:49 (4902 d 16:23 ago) Posting: # 7510 Views: 22,253 |
|
Dear all! I have a questions regarding calculation of volume of distribution at steady state (Vss). After IV bolus administration Vss can be calculated based on the non-compartmental theory as doseiv x AUMC0-infinity / AUC20-infinity. Now let us assume that the concentrations over time after extra vascular administration can be adequately described by a one-compartmental model with first order absorption and first order elimination. How can the volume of distribution at steady state be calculated under this model? Can the above formula be adjusted straightforwardly using the bioavailability F to calculate Vss = (dosepo x F x AUMC0-infinity) / AUC20-infinity? best regards Martin |
d_labes ★★★ Berlin, Germany, 2011-10-18 13:36 (4902 d 12:36 ago) @ martin Posting: # 7512 Views: 20,632 |
|
Dear Martin! The TOPFIT2.01) manual states (in the non-compartmental section): "Estimation of Vss is only possible following intravenous administration because: a) the bioavailability factor f is unknown following oral administration and b) the intrinsic MRT is needed (the intrinsic MRT is the MRT of the substance within the systemic circulation and thus corresponds to the MRT calculated from plasma data only in the case of intravenous administration)." (Emphasis by me) Formulas given: iv-bolus Vss = CL * MRT iv-infusion Vss = CL * (MRT - IT/2) where CL is the clearance, IT the infusion time and MRTintr=MRT of disposition disregarding the infusion time. If I remember the old days I had done compartmental modelling right the p.o. MRT is something like MRTpo = MRTiv + 1/ka + tlag in the one-compartmental model. Hope this helps. 1) Heinzel, Woloszczak, Thomann "TopFit 2.0 Pharmacokinetic and Pharmacodynamic Data Analysis System for the PC" Gustav Fisher Verlag, Stuttgart-Jena-New York 1993 — Regards, Detlew |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2011-10-18 18:02 (4902 d 08:10 ago) @ d_labes Posting: # 7517 Views: 20,649 |
|
Dear D. Labes! ❝ The TopFit 2.0 manual SCNR. ![]() — 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 |
javier ☆ Spain, 2016-09-21 18:47 (3102 d 07:25 ago) @ Helmut Posting: # 16664 Views: 18,470 |
|
❝ ❝ The TopFit 2.0 manual ❝ ❝ SCNR. Hi Helmut Do you know where is possible to buy this book (in amazon is not available, i fear) thanks!! |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-22 13:30 (3101 d 12:42 ago) @ javier Posting: # 16666 Views: 18,485 |
|
Nothing to fear. You really can purchase the manual from Amazon. It is just not cheap at all. Good luck. ❝ Do you know where is possible to buy this book (in amazon is not available, i fear) — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
d_labes ★★★ Berlin, Germany, 2016-09-22 14:09 (3101 d 12:03 ago) @ yjlee168 Posting: # 16667 Views: 18,416 |
|
Dear Yung-yin, ❝ Nothing to fear. You really can purchase the manual from Amazon. It is just not cheap at all. That's unbelievable! 429.99 bucks for an used exemplar ![]() Seems it is printed in gold letters. — Regards, Detlew |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-24 22:26 (3099 d 03:46 ago) @ d_labes Posting: # 16671 Views: 18,328 |
|
Dear Detlew, I am not sure if they sell the manual together with the software or not. ![]() ![]() ❝ Seems it is printed in gold letters. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
mittyri ★★ Russia, 2016-09-25 17:04 (3098 d 09:08 ago) @ yjlee168 Posting: # 16673 Views: 18,277 |
|
Dear Yung-jin, ❝ I am not sure if they sell the manual together with the software or not. if yes, you need to pray for 2 floppy disks to be still alive and also you need to order some device for reading ![]() — Kind regards, Mittyri |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2016-09-26 01:41 (3098 d 00:31 ago) @ mittyri Posting: # 16675 Views: 18,744 |
|
Hi Mittyri & Yung-jin, ❝ […] you need to pray for 2 floppy disks to be still alive… The software came on only one 3½″ floppy. If you are on a 64bit OS, you need an 32bit emulator of the 16bit DOS-environment. On my Win 7 64bit TopFit (Thomae Optimized Pharmacokinetic Fitting Program) runs in XP-mode: ![]() 429.99 USD is ridiculous. I got mine for 198 DEM in 1993. Taking inflation into account it should come for 145.43 Euros (163.26 USD). — 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 |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2016-09-26 02:17 (3097 d 23:55 ago) @ mittyri Posting: # 16680 Views: 18,252 |
|
Hi Mittyri, ❝ I erroneously interpreted this as 2 floppies: ❝ Yep: ![]() ❝ The app is less than 1.44 MB weight. Amazing! In the last century content was more important than form. Compiled Fortran rulez! — 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 |
ElMaestro ★★★ Denmark, 2016-09-26 11:43 (3097 d 14:29 ago) @ Helmut Posting: # 16683 Views: 18,142 |
|
❝ In the last century content was more important than form. Quote of the month! ![]() — Pass or fail! ElMaestro |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-26 02:18 (3097 d 23:54 ago) @ Helmut Posting: # 16681 Views: 18,277 |
|
Hi Helmut, Thanks for sharing the picture of TopFit & "gravity duration". Great. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
ElMaestro ★★★ Denmark, 2016-09-24 01:13 (3100 d 00:59 ago) @ martin Posting: # 16668 Views: 18,306 |
|
Hi all, ❝ How can the volume of distribution at steady state be calculated under this model? Can the above formula be adjusted straightforwardly using the bioavailability F to calculate Vss = (dosepo x F x AUMC0-infinity) / AUC20-infinity? Isn't the proposal by Martin quite reasonable in its simple logic if an estimate of F is available? I read the answers to his post, and while I gather there's possibly a sentiment towards "no can do!" the argument seems to be merely "because this book says so" where in actuality the book assumes implicitly that no estimate of F (and through that, MRT) is known. We don't have to be sheep, right? — Pass or fail! ElMaestro |
mittyri ★★ Russia, 2016-09-24 02:38 (3099 d 23:34 ago) @ ElMaestro Posting: # 16669 Views: 19,196 |
|
Hi ElMaestro, ❝ We don't have to be sheep, right? Certainly not. But as Detlew wisely noted, we need to know MIT I would cite another good article1 ![]() The equation for FO input is the same as given by Detlew, just another names: ![]() So without tlag and ka you cannot calculate Vss, sorry 1. Watari, N. & Benet, L.Z. Journal of Pharmacokinetics and Biopharmaceutics (1989) 17: 593. doi:10.1007/BF01071351 — Kind regards, Mittyri |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-24 22:19 (3099 d 03:53 ago) @ mittyri Posting: # 16670 Views: 18,436 |
|
Dear mittyri and Elmaestro, If we re-arrange the equation of Vss = (dosepo x F x AUMC0-infinity) / AUC20-infinity as Vss/F = (dosepo x AUMC0-infinity) / AUC20-infinity . For extravascular dosing, we only can calculate Vc/F, Vss/F, or Cl/F.❝ ... we need to know MIT,..., tlag and ka No need to know MIT (or tlag and ka). Again we can also re-arrange Vss = (F x Dose/AUC0-infinity)x MRT as Vss/F = (Dose/AUC0-infinity)x MRT = Cl x MRT .We can get the values of all parameters (Dose, AUC0-infinity, AUMC0-infinity and MRT) on the right-hand sided both equations after NCA. So I wonder why we can not calculate Vss. — All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
mittyri ★★ Russia, 2016-09-24 23:33 (3099 d 02:39 ago) @ yjlee168 Posting: # 16672 Views: 18,267 |
|
Dear Yung-jin, That's kind of incorrect. ❝ MRT = AUMC0-infinity/AUC0-infinity ❝ Again we can also re-arrange — Kind regards, Mittyri |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-26 01:27 (3098 d 00:45 ago) @ mittyri Posting: # 16674 Views: 18,368 |
|
Dear mittyri, Thanks for your response. You are correct. Apparently Vdss cannot be calculated using NCA with BE dataset alone. In WNL manual of the old version (v5.3), it said: (quoted) "An estimate of the volume of distribution at steady state. Vss = MRTINF*Cl, where MRT = Mean Residence Time and CL= total body clearance. For steady-state date (a typo? data?), Vss = MRTINF*Clss. Not computed for model 200, as calculating MRT from oral data requires estimating Mean Input Time, which requires compartmental methods." about Vdss . It is easy to calculate Vdss with IV or IV infusion since MRTiv is ready to use. For extravascular dosing (po for example), MRTpo = MRTiv + MITpo. Thus we not only require MIT (ka and tlag) but also MRTiv to calculate Vdss . BTW, I just find this R package PKNCA seems interesting. It calculates Vdss too.Finally, I have a question: when using NCA to analyze a BE dataset, we can obtain MRT. Apparently this MRT is not what we call MRTpo . What is it?— All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
mittyri ★★ Russia, 2016-09-26 01:45 (3098 d 00:27 ago) @ yjlee168 Posting: # 16676 Views: 18,584 |
|
Dear Yung-jin, ❝ Finally, I have a question: when using NCA to analyze a BE dataset, we can obtain MRT. Apparently this MRT is not what we call ![]() So in PHX interpretation MRTINFpo = MRTINF + MIT = AUMCINF/AUCINF — Kind regards, Mittyri |
Helmut ★★★ ![]() ![]() Vienna, Austria, 2016-09-26 01:47 (3098 d 00:25 ago) @ yjlee168 Posting: # 16677 Views: 18,331 |
|
Hi Yung-jin, ❝ Finally, I have a question: when using NCA to analyze a BE dataset, we can obtain MRT. Apparently this MRT is not what we call See this post. IIRC, AUMC/AUC for ev administration was sometimes called in the “old days” of PK the Gravity Duration (GD). — 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 |
yjlee168 ★★★ ![]() ![]() Kaohsiung, Taiwan, 2016-09-26 02:13 (3097 d 23:59 ago) @ mittyri Posting: # 16679 Views: 18,186 |
|
Dear mittyri, Should Eq. (8) be written as MRT = AUMC/AUC + MIT ?— All the best, -- Yung-jin Lee bear v2.9.2:- created by Hsin-ya Lee & Yung-jin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) -> here |
mittyri ★★ Russia, 2016-09-26 02:23 (3097 d 23:49 ago) @ yjlee168 Posting: # 16682 Views: 18,168 |
|
Dear Yung-jin, ❝ Should Eq. (8) be written as Well, to cut to the chase: no. ![]() I sent the article on your mobilepk mailbox, so you can see all derivations — Kind regards, Mittyri |