NONMEM Users Network Archive

Hosted by Cognigen

Re: [NMusers] Why should we avoid using micro rate constants?

From: Singla, Sumeet K <sumeet-singla_at_uiowa.edu>
Date: Tue, 5 Feb 2019 14:00:35 +0000

Thank you so much!!
These are all wonderful insights and replies and I am definitely going to ponder over it today.

Regards,
Sumeet Singla


On Feb 5, 2019, at 7:52 AM, Saeheum Song <ss.pkpdmodel_at_gmail.com<mailto:ss.pkpdmodel_at_gmail.com>> wrote:

The input data are composed of amount as dosing and concentration in plasma. Concentration is expressed as amount divided by volume of distribution. The rate constant is movement of either amount or concentration pending on modelers intention. Whence, in the modeling fitting, dosing amount needs to be converted into concentration by introduction of volume of distribution.
With introduction of the volume of distribution (K21),
K12= Q/V1, and
K21=Q/V2
Therefore by introduction of Volume (V1), system can define all other parameters.

Simply, by model fitting using micro-constant only means we are treating amount and concentration as same unit. Hence, it should be avoided. You can still fit model with micro-constant but requires defining volume and conversion of amount into concentration to do proper modeling,

Regards,

SaeHeum Song,

Independent Consultant,


On Tue, Feb 5, 2019 at 2:05 AM <janet.wade_at_telia.com<mailto:janet.wade_at_telia.com>> wrote:
Hi All,

It could also be the statistical model. If you are estimating 4 parameters then different parameterisations should be fairly equivalent if a BLOCK(4) structure is used for both parameterisations. If only the diagonal option is used, then this could be why different results/minimisations are obtained for different parameterisations.

Kind regards,
Janet


Janet R Wade, PhD
Occams
Senior Consultant



From: owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com> <owner-nmusers_at_globomaxnm.com<mailto:owner-nmusers_at_globomaxnm.com>> On Behalf Of Leonid Gibiansky
Sent: 04 February 2019 07:30
To: Singla, Sumeet K <sumeet-singla_at_uiowa.edu<mailto:sumeet-singla_at_uiowa.edu>>
Cc: nmusers_at_globomaxnm.com<mailto:nmusers_at_globomaxnm.com>
Subject: Re: [NMusers] Why should we avoid using micro rate constants?

It could be just coding error, could you show the control stream?
Thanks
Leonid

On Feb 3, 2019, at 12:44 PM, Singla, Sumeet K <sumeet-singla_at_uiowa.edu<mailto:sumeet-singla_at_uiowa.edu>> wrote:
Hello everyone!

I have a question. I was trying to build a 2-compartment PK model for marijuana use in occasional and chronic smokers. Initially, I was using providing rate constants K12 and K21 ­in PK block and it resulted in poor fitting. Then, I later changed to CL,V1, V2 , Q and it resulted in proper fitting. I was perplexed as to why I couldn’t get a proper fit by providing rate constants? I tried to look online but couldn’t find any proper explanation about when (or not) we should use micro constants in PK block to define our model in NONMEM? Does anyone has any useful insights into this?

Regards,
Sumeet Singla
Graduate Student
Dpt. of Pharmaceutics & Translational Therapeutics
College of Pharmacy- University of Iowa


Received on Tue Feb 05 2019 - 09:00:35 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com. Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.