intergender differences and consequences [Regulatives / Guidelines]

posted by mittyri – Russia, 2019-12-04 08:53  – Posting: # 20913
Views: 97

Hi Helmut,

» »   – what do you think about statement that males and females (50/50) should be enrolled, since RLD says regarding sex differences in PK? 'Otherwise the marketed formulation could be not BE for other gender'

» Differences in plasma concentrations were observed, with Cmax and AUC being approximately 3- and 2-fold higher, respectively, in females compared to males.[/indent]That confirms the observation that highly variable drugs have a flat dose-response curve (no relevant influence on efficacy despite significantly higher concentrations). Since the experts recommended males and females, go for it. Bioanalysts will like it.

I've found very interesting paper which explains the vision of experts.

The abstract does not show the essence of recommendations given in that article, so I'll try to translate it here:
The factor of intergender differences in crossover BE studies could be evaluated using CVintra and GMR evaluation stratified by gender. The extent of difference for CVintra could be established using F test with alpha=5% (95% significance level). For GMRs the difference is significant if it is more than 20%.
In case of differences discovered the results of BE study call into question since it could be ineffective for more patients than in BE study. [what kind of patients are mentioned within BE study? I don't know, but the key message is clear]
Due to high risk of that IMP administration the patients should be informed (addendum into leaflet)

The last sentence is taken from here:
Nevertheless, analysis according to sex will provide useful information that can be included in the package insert of the generic product warning patients about original by generic substitution in accordance with their sex
But Manuel Ibarra et al. did not call into the question:
The goal of our recommendation is not to restrict the commercialization of generic drugs. Average BE should be maintained as currently performed, based on the total number of subjects.

Do you remember your investigations regarding dosing groups? :-D Looks like another factor starts the game in Russia!

Kind regards,
Mittyri

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