martin ★★ Austria, 20111018 09:49 (4359 d 18:45 ago) Posting: # 7510 Views: 19,205 

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 noncompartmental theory as dose_{iv} x AUMC_{0infinity} / AUC^{2}_{0infinity}. Now let us assume that the concentrations over time after extra vascular administration can be adequately described by a onecompartmental 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 = (dose_{po} x F x AUMC_{0infinity}) / AUC^{2}_{0infinity}? best regards Martin 
d_labes ★★★ Berlin, Germany, 20111018 13:36 (4359 d 14:58 ago) @ martin Posting: # 7512 Views: 17,857 

Dear Martin! The TOPFIT2.0^{1)} manual states (in the noncompartmental 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: ivbolus Vss = CL * MRT ivinfusion Vss = CL * (MRT  IT/2) where CL is the clearance, IT the infusion time and MRT_{intr}=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 MRT_{po} = MRT_{iv} + 1/k_{a} + t_{lag} in the onecompartmental model. Hope this helps. ^{1) }Heinzel, Woloszczak, Thomann "TopFit 2.0 Pharmacokinetic and Pharmacodynamic Data Analysis System for the PC" Gustav Fisher Verlag, StuttgartJenaNew York 1993 — Regards, Detlew 
Helmut ★★★ Vienna, Austria, 20111018 18:02 (4359 d 10:32 ago) @ d_labes Posting: # 7517 Views: 17,925 

Dear D. Labes! ❝ The TopFit 2.0 manual SCNR. — Diftor 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, 20160921 18:47 (2559 d 09:47 ago) @ Helmut Posting: # 16664 Views: 15,765 

❝ ❝ 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, 20160922 13:30 (2558 d 15:04 ago) @ javier Posting: # 16666 Views: 15,773 

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,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
d_labes ★★★ Berlin, Germany, 20160922 14:09 (2558 d 14:25 ago) @ yjlee168 Posting: # 16667 Views: 15,672 

Dear Yungyin, ❝ 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, 20160924 22:26 (2556 d 06:08 ago) @ d_labes Posting: # 16671 Views: 15,609 

Dear Detlew, I am not sure if they sell the manual together with the software or not. If not, it is really expensive. ❝ Seems it is printed in gold letters. — All the best,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
mittyri ★★ Russia, 20160925 17:04 (2555 d 11:31 ago) @ yjlee168 Posting: # 16673 Views: 15,554 

Dear Yungjin, ❝ 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, 20160926 01:41 (2555 d 02:53 ago) @ mittyri Posting: # 16675 Views: 16,029 

Hi Mittyri & Yungjin, ❝ […] 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 DOSenvironment. On my Win 7 64bit TopFit (Thomae Optimized Pharmacokinetic Fitting Program) runs in XPmode: 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). — Diftor 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, 20160926 02:17 (2555 d 02:17 ago) @ mittyri Posting: # 16680 Views: 15,539 

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! — Diftor 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, 20160926 11:43 (2554 d 16:51 ago) @ Helmut Posting: # 16683 Views: 15,441 

❝ In the last century content was more important than form. Quote of the month! — Pass or fail! ElMaestro 
yjlee168 ★★★ Kaohsiung, Taiwan, 20160926 02:18 (2555 d 02:16 ago) @ Helmut Posting: # 16681 Views: 15,565 

Hi Helmut, Thanks for sharing the picture of TopFit & "gravity duration". Great. — All the best,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
ElMaestro ★★★ Denmark, 20160924 01:13 (2557 d 03:21 ago) @ martin Posting: # 16668 Views: 15,569 

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 = (dose_{po} x F x AUMC_{0infinity}) / AUC^{2}_{0infinity}? 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, 20160924 02:38 (2557 d 01:56 ago) @ ElMaestro Posting: # 16669 Views: 16,429 

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 article^{1} The equation for FO input is the same as given by Detlew, just another names: So without t_{lag} and k_{a} you cannot calculate V_{ss}, 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, 20160924 22:19 (2556 d 06:15 ago) @ mittyri Posting: # 16670 Views: 15,672 

Dear mittyri and Elmaestro, If we rearrange the equation of Vss = (dose_{po} x F x AUMC_{0infinity}) / AUC^{2}_{0infinity} as Vss/F = (dose_{po} x AUMC_{0infinity}) / AUC^{2}_{0infinity} . For extravascular dosing, we only can calculate Vc/F, Vss/F, or Cl/F.❝ ... we need to know MIT,..., t_{lag} and k_{a} No need to know MIT (or t_{lag} and k_{a}). Again we can also rearrange Vss = (F x Dose/AUC_{0infinity})x MRT as Vss/F = (Dose/AUC_{0infinity})x MRT = Cl x MRT .We can get the values of all parameters (Dose, AUC_{0infinity}, AUMC_{0infinity} and MRT) on the righthand sided both equations after NCA. So I wonder why we can not calculate Vss. — All the best,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
mittyri ★★ Russia, 20160924 23:33 (2556 d 05:01 ago) @ yjlee168 Posting: # 16672 Views: 15,559 

Dear Yungjin, That's kind of incorrect. ❝ MRT = AUMC_{0infinity}/AUC_{0infinity} ❝ Again we can also rearrange — Kind regards, Mittyri 
yjlee168 ★★★ Kaohsiung, Taiwan, 20160926 01:27 (2555 d 03:07 ago) @ mittyri Posting: # 16674 Views: 15,585 

Dear mittyri, Thanks for your response. You are correct. Apparently Vd_{ss} 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 steadystate 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 Vd_{ss} . It is easy to calculate Vd_{ss} with IV or IV infusion since MRT_{iv} is ready to use. For extravascular dosing (po for example), MRT_{po} = MRT_{iv} + MIT_{po}. Thus we not only require MIT (k_{a} and t_{lag}) but also MRT_{iv} to calculate Vd_{ss} . BTW, I just find this R package PKNCA seems interesting. It calculates Vd_{ss} 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 MRT_{po} . What is it?— All the best,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
mittyri ★★ Russia, 20160926 01:45 (2555 d 02:49 ago) @ yjlee168 Posting: # 16676 Views: 15,771 

Dear Yungjin, ❝ 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 MRTINF_{po} = MRTINF + MIT = AUMCINF/AUCINF — Kind regards, Mittyri 
Helmut ★★★ Vienna, Austria, 20160926 01:47 (2555 d 02:47 ago) @ yjlee168 Posting: # 16677 Views: 15,574 

Hi Yungjin, ❝ 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). — Diftor 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, 20160926 02:13 (2555 d 02:22 ago) @ mittyri Posting: # 16679 Views: 15,492 

Dear mittyri, Should Eq. (8) be written as MRT = AUMC/AUC + MIT ?— All the best,  Yungjin Lee bear v2.9.1: created by Hsinya Lee & Yungjin Lee Kaohsiung, Taiwan https://www.pkpd168.com/bear Download link (updated) > here 
mittyri ★★ Russia, 20160926 02:23 (2555 d 02:11 ago) @ yjlee168 Posting: # 16682 Views: 15,475 

Dear Yungjin, ❝ 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 