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Dear all,
I heard that lipophilic compounds could act as a detergent for
microsomes
vesicles and therefore inhibit CYP activities.
Until now, I was not able to find any references mentionning this point.
Has anybody heard of this? if yes, I would appreciate some literature.
regards,
francois busquet
--
Francois BUSQUET
Merck KGaA
NCD/ TOX DA, U9/2111
Frankfurter Str. 250
D-64271 Darmstadt
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I would think that depends entirely on whether the compound has space
separation between charge and hydrophobic part, like in lipid
molecules. Some of these type of compounds may even cause
phospholipidosis at therapeutic concentration ranges.
Anyway, some examples: Benzalkonium chloride is an example and
dimethyldioctadecyl-ammonium bromide as well. Two quaternary ammonium
compounds that can have a nasty effect at too high dose (they are in
effect antibacterials I believe)
regards
Hans
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Dear Francois,
I can't help you with literature data, however, I can confirm that some
ionized lipophilic compounds can act as surfactants in high
concentrations, for example 100 micro molar and above. This can
significantly influence activity of membrane-associated enzymes like
CYPs and UGTs. The effect would present itself as a substrate inhibiton
or activation.
Regards, Jurij Trontelj
Faculty of pharmacy
University of Ljubljana
Askerceva 7
1000 Ljubljana, Slovenia
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Dear Francois
You might find the following two articles and references
therein of interest:
Buggins 2007 The effects of pharmaceutical excipients on drug
disposition. Adv Drug Delivery Reviews 59 1482-1503.
Anna Seelig & Gregori Gerebtzoff (2006) Enhancement of drug absorption
by noncharged detergents through membrane and P-glycoprotein binding.
Expert Opinion on Drug Metabolism & Toxicology 2, 5, 733-752.
Regards
David Turner
--
David Turner PhD
Senior Scientist
Simcyp Limited, Blades Enterprise Centre, John Street, Sheffield S2
4SU UK
http://www.simcyp.com
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