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Unable to capture high Cmax after IV bolus dose, all the parameters used were similar between simcyp and PK SIM, but couldnt capture high Cmax in PK SIM? #250

Closed REVATHICHAPA closed 5 years ago

PavelBal commented 5 years ago

I am afraid we need more information on what you are trying to model. I do not think you should expect identical results when using the different models of PK-Sim and SimCyp.

REVATHICHAPA commented 5 years ago

The model is not different in any way. I am unable to get the high Cmax for IV Bolus dose. The Cmax prediction was very low. How do I improvise my prediction of Cmax?

msevestre commented 5 years ago

As mentioned by @PavelBal, you need to provide us with some context if you would like anyone to help. If you can, upload the project so that someone can have a look at it

Aedginto commented 5 years ago

Not hitting the Cmax of an IV bolus or infusion is very likely a distribution volume issue. If your predicted is lower than observed, the V is predicted to be too high. V is a function of tissue volumes (unlikely to be the problem), fraction unbound in plasma and tissue: plasma partition coefficients. How was V determined in the SimCyp model. Was V an input in SimCyp or was did you use a Kp algorithm (without adjustment) to predict tissue: plasma partition coefficients? If a Kp algorithm was used, are you using the same one in PK-Sim?

REVATHICHAPA commented 5 years ago

I used method II/Rodgers method in both the models.

REVATHICHAPA commented 5 years ago

I havent had any scalar in Simcyp, it looks like i need to adjust scalar in PKSIM to get the Cmax. Why is that so?

Aedginto commented 5 years ago

What is the fraction unbound in plasma? Is it low?

tobiasK2001 commented 5 years ago

and what plasma concentration are you comparing to SimCyp: "Venous blood plasma" or "Peripheral venous blood plasma"?

fredsevmartins commented 5 years ago

If everything is similar the problem could be with the number of points that your pk curve has ( conc vs time). By defaunt Simcyp plot all grafics with 2000 blood sampling that should be enough to 24hr simulation. So if you have 3 days simulation maybe you will miss some points. Try to increase this number in PKSim if possible.Like @Tobiask2001 suggested it could be the problem.

REVATHICHAPA commented 5 years ago

yes it is 0.05

REVATHICHAPA commented 5 years ago

I am comparing peripheral venous blood concentrations?

fredsevmartins commented 5 years ago

Depends, you can do both. Please check what option you set.

StephanSchaller commented 5 years ago

Best compare venous blood first.

Depending on the permeability measures, once in peripheral VB, the drug may already be mixed with interstitial and thus exposed to a higher volume of distribution. Thus you should also compare permeability measures for plasma <-> interstitial (endothelial permeability)

Yuri05 commented 5 years ago

Closing the issue. @REVATHICHAPA Please reopen if you have any further questions on this topic