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Dear all
I have a general query regarding the fasting in multiple dose BE study. In case of multiple Dose (MD) steady state BE studies in patients, the blood collection is generally performed after last dose or in between when steady state has been supposed to be achieved. My query is that:
1. Is there any need of fasting in such study, even if not mentioned in FDA or any other guidelines?
2. If fasting has to be done, on which day it should be done (1st day of dosing or on the day of blood sampling)?
thanks in advance
regards
-- RAVI KANT BHATIA
Research Associate-PK/PD
Clinsys Clinical Research Ltd.
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Dear Ravi:
For bio-equivalence study, single dose study is the desirable study design because small changes in the absorption of the drug is more sensitive after single dose then under steady state conditions.
It is true that patients hardly take single dose of the drug so it is tempting to conclude that bio-equivalence at steady state is clinically more meaningful then the study conducted after sinle doses. This is however not the case.
Having done the single dose study under fasting and fed state I would recommend to do the PK of the drug/formulation after multiple dose study since the multiple dose PK parameters [Cmin(ss), Cmax(ss), Fluctuation(ss), AUC (0-tau)(ss), CL/F(ss)] are more relevant clinically but not evaluation of a new dosage form. I normally I evaluate food effect response after single dose and then conduct mutiple dose study based on the results of the single dose studu.. This approach is most advisable if you are dealing with modified-release dosage form and there is a substantial (increase or decrease) food effect reponse..
So single dose study is for accurately assessing bio-equivalence of test and reference formulations while the multiple dose study is to evaluate ewheter fasinfg or fed dosing will give consistent and repoduciblely high systemic exposure of the drug. This is necessary for dosing recommendation especially with mofified-release dosage forms..
Hope the help,
Aziz
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The following message was posted to: PharmPK
Dear Ravi,
Multiple dose study is recommended especially for modified-release dosage forms. Food affect may have some effect in its absorption hence in BE studies is not recommended much.
Multiple dose: Is to evaluate reproducible high systemic exposure of the drug (fasting or fed dosing). In single dose: Bio-equivalence of test and reference formulations will assess.
If at al if you want to do multi-dose fasting study, it should be before 1st day of dosing.
Regards,
Sudipta Basu
Senior Research Scientist (DMPK)
Sai Advantium Pharma Ltd.,
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