PKBR
☆    

Brazil,
2019-01-30 01:58
(edited by mittyri on 2019-01-30 12:50)

Posting: # 19825
Views: 434
 

 Simulation plasma and tissue profile [PK / PD]

I'd like to ask about simulation.
1. I have one dose data (named D1, single dose) from plasma (total concentration) and from tissue (free concentration), as well as data from another dose (named D2, multiple dose) for tissue but not for plasma. After non-compartmental analysis of the data, there was no statistically significant difference for half-life between plasma (D1) and tissue (D1 and D2) by ANOVA. AUC / Dose by D1 and D2 also had no difference. Given the value of binding to plasma proteins and having the free concentration profiles for D1 and D2, would it be possible to calculate the total plasma concentration of D2 for each point, considering the free concentration in this dose at each time?

2. If it is possible, and with total plasma concentration profile projected for D2, could we use compartmental analysis and, following two compartments, obtain A, B, alpha and beta macro-constants? From this point on, could we simulate other multiple dosing schedules (changing the interval between doses)?

I do not know if it is possible to make these assumptions ... could anyone clarify these questions?

Kind regards!
PKBR.


Edit: Category changed; see also this post #1. [Mittyri]
mittyri
★★  

Russia,
2019-01-31 23:01
(edited by mittyri on 2019-01-31 23:30)

@ PKBR
Posting: # 19834
Views: 335
 

 Try to find suitable PK model

Hi,

» 1. Given the value of binding to plasma proteins and having the free concentration profiles for D1 and D2, would it be possible to calculate the total plasma concentration of D2 for each point, considering the free concentration in this dose at each time?

I would recommend to use some NONMEM/NLME/Monolix/Matlab/R skills to build an appropriate model(s). The model building process is not straightforward sometimes, but in case of success (successful validation and other signs of goodness of predicability) you'll get what you want.

» 2. If it is possible, and with total plasma concentration profile projected for D2, could we use compartmental analysis and, following two compartments, obtain A, B, alpha and beta macro-constants? From this point on, could we simulate other multiple dosing schedules (changing the interval between doses)?
The main question is: are you sure that 2-cmt model is applicable for your analyte? Are there any other investigations regarding that statement?
As I answered for the 1st question, if the model is finalized (so, the modeller realized that it suites the data well and have enough predicability level), all other questions are just peanuts for the modeller.

Kind regards,
Mittyri
Activity
 Thread view
Bioequivalence and Bioavailability Forum |  Admin contact
19,604 posts in 4,158 threads, 1,340 registered users;
online 8 (0 registered, 8 guests [including 6 identified bots]).
Forum time (Europe/Vienna): 17:39 CEST

Nothing in the world is more dangerous
than sincere ignorance
and conscientious stupidity.    Martin Luther King, Jr.

The BIOEQUIVALENCE / BIOAVAILABILITY FORUM is hosted by
BEBAC Ing. Helmut Schütz
HTML5