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Beholder ★ Russia, 2013-11-12 15:02 (4197 d 03:10 ago) Posting: # 11870 Views: 6,462 |
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Dear All, Could you please clarify is it possible to compare PK parameters or make up a conclusion about bioequivalence for immediate and modified release tablets? Thank you in advance. Edit: Category changed. [Helmut] — Best regards Beholder |
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Dr_Dan ★★ Germany, 2013-11-13 12:31 (4196 d 05:41 ago) @ Beholder Posting: # 11874 Views: 5,394 |
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Dear Beholder Modified release forms are developed based on the rationale that there is a relationship between the pharmacological/toxicological response and the characteristics of systemic exposure to the active substance/metabolite(s). The aim of the modified release formulation is therefore, in most cases, to reach a similar total exposure (AUC) to active substance as for the immediate release formulation. This does not necessitate that the same nominal doses are given (the modified release formulation may have a different extent of absorption). In general modified-release formulations are not bioequivalent to their immediate release form. Consequently PK data alone may not be sufficient for evaluating whether the benefit/risk ratio of the modified release formulation is comparable to the corresponding doses of the immediate release form. Therefore additional clinical data will generally be required. I hope this helps. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
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jag009 ★★★ NJ, 2013-11-14 00:03 (4195 d 18:10 ago) @ Beholder Posting: # 11879 Views: 5,385 |
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Hi, Are you referring to one IR table to one ER tablet? If so, no because that's not really the intent of a MR product. MR product has a slower rate of drug release -> 1) aim to lower the incidence of adverse events, 2) to provide a once daily blood level coverage (24 hrs). Now I have seen submission in which BE was demonstrated between 1 MR tablet vs IR tablets given several times daily. Yes meeting the 90% CIs for AUC and Cmax. It was a 505(b)2 filing. John |
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luvblooms ★★ India, 2013-11-14 09:16 (4195 d 08:57 ago) @ jag009 Posting: # 11883 Views: 5,524 |
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Hey Beholder It totally depends upon intention of development. Let's say if you want to keep exposure (AUC) same but reduce the Cmax (to decrease the fluctuation/toxicity/side effects) you can go for proving equivalence in term of AUC between one IR and ER. But as John has rightly said, it would be treated either as 505 (B) 2 or a different NDA (where you have to prove clinical efficacy as well. A typical example of this is Modified Release (MR) tacrolimus which is an extended release formulation of tacrolimus (Prograf) administered once daily in the morning. In healthy volunteers, the MR tacrolimus formulation given qd AM and Prograf administered twice daily (bid) have a similar exposure (AUC) and trough levels (Cmin), with a reduced peak level (Cmax) ![[image]](img/uploaded/image67.jpg) So if you are planning to do a bioequivalence study between an IR and MR (for any reason) you should try to match exposure/AUC with IR product not the Cmax. Regards — ~A happy Soul~ |
Ing. Helmut Schütz