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RegisterPrediction of Cmax [Dissolution / BCS / IVIVC]
dear luvblooms !
your mean concentration time profile for your preparations look like the drug is given by an extravascular route of administration (oral, rectal, ... ).
1) you have to find an adequate mathematical model for your data. as starting point you may use a simple one-compartmental open model with first order absorption and first order elimination (e.g. Gibaldi and Perrier 1982, pages 34) which has the form
c = ((ka x F x D) / (V x (ka-ke))) x (exp(-ke x t)-exp(-ka x t))
where c represents the measured concentration, F represent the fraction absorbed, ka represent the absorption rate, D represents the dose administered, ke represent the elimination rate, V represent the volume of distribution and t represent the time. as you can see from this model, an increased release - on the assumption that dose, volume of distribution and elimination rate are not affected - can be caused by an increased absorption rate (ka) and/or and increased fraction absorbed (0<=F<=1).
2) estimate parameters based on observed data for an adequate model using nonlinear fitting. from a technical point of view you may have to a-priori specify V, D and F as the nonlinear fitting algorithm may not be able to distinguish between these parameter using the closed form of the model stated above (nonlinear fitting is mixture between science and art !!).
3) replace the estimated absorption rate and/or fraction absorbed (or rather the product F x D) with your assumptions and plot / re-calculate concentrations at various time points with modified parameters. using this approach you can check different scenarios and how this scenarios affect Cmax or any other concentration (summarized by the AUC).
on the assumptions stated above, I think that
- an increased absorption rate may affect Tmax but not Cmax
- an increased fraction absorbed may affect Cmax but not Tmax (curve is simply shifted)
- an increased absorption rate and an increased fraction absorbed may affect Cmax and Tmax
hope this helps
martin
your mean concentration time profile for your preparations look like the drug is given by an extravascular route of administration (oral, rectal, ... ).
1) you have to find an adequate mathematical model for your data. as starting point you may use a simple one-compartmental open model with first order absorption and first order elimination (e.g. Gibaldi and Perrier 1982, pages 34) which has the form
c = ((ka x F x D) / (V x (ka-ke))) x (exp(-ke x t)-exp(-ka x t))
where c represents the measured concentration, F represent the fraction absorbed, ka represent the absorption rate, D represents the dose administered, ke represent the elimination rate, V represent the volume of distribution and t represent the time. as you can see from this model, an increased release - on the assumption that dose, volume of distribution and elimination rate are not affected - can be caused by an increased absorption rate (ka) and/or and increased fraction absorbed (0<=F<=1).
2) estimate parameters based on observed data for an adequate model using nonlinear fitting. from a technical point of view you may have to a-priori specify V, D and F as the nonlinear fitting algorithm may not be able to distinguish between these parameter using the closed form of the model stated above (nonlinear fitting is mixture between science and art !!).
3) replace the estimated absorption rate and/or fraction absorbed (or rather the product F x D) with your assumptions and plot / re-calculate concentrations at various time points with modified parameters. using this approach you can check different scenarios and how this scenarios affect Cmax or any other concentration (summarized by the AUC).
on the assumptions stated above, I think that
- an increased absorption rate may affect Tmax but not Cmax
- an increased fraction absorbed may affect Cmax but not Tmax (curve is simply shifted)
- an increased absorption rate and an increased fraction absorbed may affect Cmax and Tmax
hope this helps
martin
Complete thread:
- Prediction of Cmax luvblooms 2008-07-22 06:43
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Prediction of Cmax martin 2008-07-23 10:24
- Prediction of Cmax luvblooms 2008-07-24 05:57
- Prediction of Cmaxmartin 2008-07-24 09:56
- Prediction of Cmax Helmut 2008-07-24 14:18
- Prediction of Cmax martin 2008-07-25 08:48
- Prediction of Cmax Helmut 2008-07-24 14:18
- Prediction of Cmaxmartin 2008-07-24 09:56
- Prediction of Cmax luvblooms 2008-07-24 05:57
- Prediction of Cmax martin 2008-07-23 10:24
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