Back to the Top
We have an oral formulation of magnesium and are seeking marketing approval for use in
hypomagnaesmia.
The intravenous formulation is approved and the oral form has been used on licence for more than 20
years (no oral form has been approved).
There is no information on bioavailability of the oral formulation of this supplement.
We are proposing to carry out a cross-over study (iv vs. oral) in healthy volunteers to assess the
absolute oral bioavailability.
We would base the assessment on unadjusted and pre-dose adjusted (incremental) serum concentrations
(subject's diet would be controlled throughout the study).
The PK of magnesium has been estimated in man (CL 4 L/h, Vss 30 L) following intravenous magnesium
supplementation.
We would have some idea of inter-subject variability after iv and oral dosing so can estimate
appropriate sample size.
What could be the limitations of this study to support an approval?
Any advice welcomed!
Regards,
Charlie
Charlie Brindley
KinetAssist Ltd
Back to the Top
The strongest limitations could be the low bioavailability and the interference of gastric empting.
It should be I'm wrong, however magnesium should be absorbed by carrier-mediated transport and only
in a limited portion of small intestine. Food could also be an issue, together with transit time in
the small intestine.
Kind regards
Stefano
Back to the Top
Dear Charlie,
We worked on this issues several years ago. In a classic bioavailability study, you have the risk of
not seeing any increase of magnesium serum concentrations (since the tissular pool collects the
majority of the exogenous magnesium and not the bloodstream). We had addressed this issue by using
stable isotope-enriched magnesium for either oral and iv route and were able to accurately measured
bioavailability from plasma and urines (see this paper Pharm Res. 1998 Feb;15(2):347-51. Use of the
stable isotopes technique to evaluate the bioavailability of a pharmaceutical form of magnesium in
man. Benech H. et al.).
Hope this help.
Henri Benech
|
Want to post a follow-up message on this topic?
If this link does not work with your browser send a follow-up message to PharmPK@lists.ucdenver.edu with "Oral magnesium supplementation" as the subject |
Copyright 1995-2014 David W. A. Bourne (david@boomer.org)