All documents - European Patent Register (epo.org) The following...

All documents - European Patent Register (epo.org)

The following extracts are taken from the Text approved by the Examiner for Grant

“It will be understood that the objective of the manufacture process is not to admix, or to mingle, or to blend the suppository base with the isoflavonoid as generally occurs in pharmacy practice of admixing components, as it is believed that the resulting admixture would have a lower likelihood of providing therapeutic benefit in this context.

“Typically the suppository, pessary or like device for use according to the invention is substantially hydrophobic or lipophilic throughout and does not contain a hydrophilic foci or region formed from the ligation or complexing of the isoflavonoid to or with another pharmaceutical compound, carrier or excipient.

“In a preferred embodiment, all of the isoflavonoid added to a dosage unit is dissolved in the base. In this embodiment, no isoflavonoid is left in admixture with the suppository base. This is believed to increase the likelihood of the uptake of all of the isoflavonoid given in the dosage unit.

CONCLUSIONS
Rectal and oral dosage delivery of idronoxil delivered approximately similar levels of ‘free’ (bio-active) idronoxil. However, oral delivery delivered the drug in this desirable form on a pulsatile basis, producing a higher Cmax, but with a half life of about 45 minutes that saw drug levels substantially fall within 2-3 hours and to be a sub-therapeutic levels before 4 hours. In contrast, rectal delivery maintained therapeutic levels of free idronoxil in the blood for at least 8 hours, and at the same time exposing the drug to a substantially lower level of Phase 2 metabolism. Given that the mechanism of action of idronoxil as a chemo-sensitiser or radio-sensitiser is dependent on a sustained presence of the drug in the blood, the rectal delivery of idronoxil obviates the need for repeat dosing, with repeat dosing being from 8 to 26 hours from a previous administration depending on the mg/kg dose of idronoxil given in the previous administration. This compares highly favourably with oral delivery where repeat dosings would be required every approximately 3-4 hours irrespective of whether a 5 to 20 mg/kg dose is given. This outcome with the rectal delivery is a highly desirable PK characteristic for idronoxil when used as a chemo- or radio-sensitiser.