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ioanam ★ Romania, 2013-09-07 23:55 (4672 d 13:55 ago) (edited on 2013-09-09 10:15) Posting: # 11461 Views: 4,147 |
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Dear all, I have a question about a bioequivalence study for nicergoline. Nicergoline is not quantifiable in plasma, but both metabolites MMDL and MDL are detectable. According to EMA regulation, which of the metabolites should be analyzed? My opinion is that for both of them must be performed the statistics. Am I wrong? Thank you for advice. Ioana Edit: Category changed. [Dr_Dan] |
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Dr_Dan ★★ Germany, 2013-09-09 12:15 (4671 d 01:36 ago) @ ioanam Posting: # 11462 Views: 3,399 |
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Dear Ioana Since 10-Methoxydihydrolysergol (MDL) and 1-Methyl-10-Methoxydihydrolysergol (1-MMDL) are both active I would suggest to evaluate both of them. However, according to CPMP/QWP/EWP/1401/98 Rev. 1 "Due to recent developments in bioanalytical methodology it is unusual that parent drug cannot be measured accurately and precisely." Bioequivalence studies for nicergoline using metabolites are quite old (e.g. CT-Pharma BE study conducted in 1986). After dosing of 70 μg/kg of radiolabelled nicergoline an activity was detected which corresponded to a plasma level of 100 - 200 ng/ml (SmPC Nicergolin-CT 10 mg Filmtabletten). So I would try to find out if you could develop an analytical method which would be sensitiv enough to detect the parent drug. Kind regards Dan — Kind regards and have a nice day Dr_Dan |
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ioanam ★ Romania, 2013-09-10 16:42 (4669 d 21:08 ago) @ Dr_Dan Posting: # 11468 Views: 3,414 |
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Dear Dan Thank you very much for your response. In case of nicergoline, we found data that revealed that nicergoline undergoes an important first - pass effect and can not be detected in plasma samples. Therefore, I am planning to use both metabolites. From my experience, the metabolite data is used only as supportive data. This is the reason for my question (and I hope that my question is corect) In case of analysis of more than one metabolite, the bioequivalence criteria must be met by all metabolites? (now is the case of nicergoline, but also is a theoretical question) Thank you Ioana Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Helmut] |
Ing. Helmut Schütz