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RegisterProbably based on PK/PD modelling [Regulatives / Guidelines]
Hi John,
I don't have an answer to your question, but I've found an abstract from FDA that can lift the veil a little bit.
Please look through this hodgepodge:
Abstracts Accepted for American Conference on Pharmacometrics 2015
And you cand find this one:
Assessment of Partial AUC Requirement for Bioequivalence Evaluation of Methylphenidate Hydrochloride Extended-Release Oral Suspension by Nan Zheng and Lanyan (Lucy) Fang from FDA.
What's inside the box:
We evaluated the sensitivity of PK (Cmax, AUC0-t, AUC0-3, AUC3-7, AUC7-12 and AUC3-24) and PD (Effmax, AUEC0-t, AUEC0-3, AUEC3-7, AUEC7-12 and AUEC3-24) endpoints in response to formulation changes. With the formulationspecific model parameters varied for the test formulation, we calculated the test-to-reference ratios of these PK and PD parameters in a typical study subject, and calculated the chances of passing when bioequivalence testing was based on Cmax, AUC0-t, AUC0-3, AUC3-7, AUC7-12 and AUC3-24, in simulated single-dose, 2-sequence, 2-treatment bioequivalence studies.
<...>
Dose level, fraction of total dose, lag time and absorption rate for the first order absorption, lag time and duration for the zero order absorption, were identified as the formulation-specific model parameters. PK endpoints are in general more sensitive than PD endpoints to changes in formulation-specific model parameters. For example, values of all PK endpoints increase proportionally with dose while PD endpoints exhibit less than dose proportional increase. AUC0-3 and AUC7-12 are more sensitive than AUC0-t to changes in most of formulation-specific model parameters.
Conclusions: Because rapid onset and sustained exposure up to 12 h are important to achieve desirable therapeutic outcome for Quillivant XR and because partial AUCs are more sensitive to formulation
specific parameter changes than the conventional metrics of Cmax and AUC, we recommend using partial AUCs in bioequivalence evaluation of generic MPH extended-release oral suspension.
I don't have an answer to your question, but I've found an abstract from FDA that can lift the veil a little bit.
Please look through this hodgepodge:
Abstracts Accepted for American Conference on Pharmacometrics 2015
And you cand find this one:
Assessment of Partial AUC Requirement for Bioequivalence Evaluation of Methylphenidate Hydrochloride Extended-Release Oral Suspension by Nan Zheng and Lanyan (Lucy) Fang from FDA.
What's inside the box:
We evaluated the sensitivity of PK (Cmax, AUC0-t, AUC0-3, AUC3-7, AUC7-12 and AUC3-24) and PD (Effmax, AUEC0-t, AUEC0-3, AUEC3-7, AUEC7-12 and AUEC3-24) endpoints in response to formulation changes. With the formulationspecific model parameters varied for the test formulation, we calculated the test-to-reference ratios of these PK and PD parameters in a typical study subject, and calculated the chances of passing when bioequivalence testing was based on Cmax, AUC0-t, AUC0-3, AUC3-7, AUC7-12 and AUC3-24, in simulated single-dose, 2-sequence, 2-treatment bioequivalence studies.
<...>
Dose level, fraction of total dose, lag time and absorption rate for the first order absorption, lag time and duration for the zero order absorption, were identified as the formulation-specific model parameters. PK endpoints are in general more sensitive than PD endpoints to changes in formulation-specific model parameters. For example, values of all PK endpoints increase proportionally with dose while PD endpoints exhibit less than dose proportional increase. AUC0-3 and AUC7-12 are more sensitive than AUC0-t to changes in most of formulation-specific model parameters.
Conclusions: Because rapid onset and sustained exposure up to 12 h are important to achieve desirable therapeutic outcome for Quillivant XR and because partial AUCs are more sensitive to formulation
specific parameter changes than the conventional metrics of Cmax and AUC, we recommend using partial AUCs in bioequivalence evaluation of generic MPH extended-release oral suspension.
—
Kind regards,
Mittyri
Kind regards,
Mittyri
Complete thread:
- New Guidance - Methylphenidate jag009 2016-02-02 20:16 [Regulatives / Guidelines]
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- New Guidance - Methylphenidate Helmut 2016-02-03 14:10
- New Guidance - Methylphenidate jag009 2016-02-03 22:53
- Probably based on PK/PD modellingmittyri 2016-02-04 23:35
- Probably based on PK/PD modelling jag009 2016-02-05 23:00
- New Guidance - Methylphenidate Helmut 2016-02-03 14:10
Ing. Helmut Schütz