Prolonged release: sampling time and washout calculation [Design Issues]
Dear All,
Could you please help me with the sampling time and sufficient washout calculation for prolonged release formulation.
According EMA (and russian) GL:
At least three to four samples are needed during the terminal log-linear phase in order to reliably estimate the terminal rate constant (which is needed for a reliable estimate of AUC(0-∞)).
Do I understand it right, that at least 3 points should be planned after the ending of absorption? What kind of parameters should I take into account for sampling time calculation?
For example: according to the literature data the absorption ends up in 20h, so should we add at least 3 timepoints after 20h to be able to calculate the terminal rate constant?
GL about washout period:
The treatment periods should be separated by a wash out period sufficient to ensure that drug concentrations are below the lower limit of bioanalytical quantification in all subjects at the beginning of the second period. Normally at least 5 elimination half-lives are necessary to achieve this.
I'm unable to make head nor tail of different types of halflives
We have halflife of API (derived from IV profile in originator's studies), halflife of prolonged release formulation (from other BEQ studies), apparent halflife (from originator's PK studies).
Which type of halflife should be used for washout calculation?
Could you please help me with the sampling time and sufficient washout calculation for prolonged release formulation.
According EMA (and russian) GL:
At least three to four samples are needed during the terminal log-linear phase in order to reliably estimate the terminal rate constant (which is needed for a reliable estimate of AUC(0-∞)).
Do I understand it right, that at least 3 points should be planned after the ending of absorption? What kind of parameters should I take into account for sampling time calculation?
For example: according to the literature data the absorption ends up in 20h, so should we add at least 3 timepoints after 20h to be able to calculate the terminal rate constant?
GL about washout period:
The treatment periods should be separated by a wash out period sufficient to ensure that drug concentrations are below the lower limit of bioanalytical quantification in all subjects at the beginning of the second period. Normally at least 5 elimination half-lives are necessary to achieve this.
I'm unable to make head nor tail of different types of halflives
We have halflife of API (derived from IV profile in originator's studies), halflife of prolonged release formulation (from other BEQ studies), apparent halflife (from originator's PK studies).
Which type of halflife should be used for washout calculation?
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Kind regards,
Mittyri
Kind regards,
Mittyri
Complete thread:
- Prolonged release: sampling time and washout calculationmittyri 2014-12-21 17:52 [Design Issues]
- Prolonged release: sampling time and washout calculation ElMaestro 2014-12-21 20:38
- Prolonged release: sampling time and washout calculation AngusMcLean 2014-12-21 23:00
- Predominant t½ Helmut 2014-12-22 02:43
- Prolonged release: updated data mittyri 2014-12-28 16:37
- Prolonged release: updated data ElMaestro 2014-12-28 17:23
- Prolonged release: updated data mittyri 2014-12-29 07:57
- Prolonged release: updated data AngusMcLean 2014-12-29 00:00
- Prolonged release: washout mittyri 2014-12-29 08:32
- Prolonged release: washout AngusMcLean 2014-12-29 15:29
- Prolonged release: thanks mittyri 2014-12-29 21:11
- Prolonged release: washout AngusMcLean 2014-12-29 15:29
- Prolonged release: washout mittyri 2014-12-29 08:32
- Prolonged release: updated data ElMaestro 2014-12-28 17:23
- Prolonged release: updated data mittyri 2014-12-28 16:37