Eur J Pharm Sci. 1999 Aug;8(4):255-60.  

Estimation of flavin-containing monooxygenase activity in intact hepatocyte
monolayers of rat, hamster, rabbit, dog and human by using N-oxidation of
benzydamine.

Ubeaud G, Schiller CD, Hurbin F, Jaeck D, Coassolo P.

F. Hoffmann-La Roche Ltd., Pharma Division, Preclinical Research, Basel,
Switzerland. ubeaud@pharma.u-strasbg.fr

The flavin-containing monooxygenase (FMO)-dependent N-oxidation of benzydamine
has been assessed as a method for monitoring the activity of FMOs in monolayer
cultures of hepatocytes from rat, dog, rabbit, hamster and human. The advantage
of this substrate is that benzydamine N-oxide formation can be measured directly
in extracts of cellular incubations without an intensive work-up procedure.
Benzydamine and its N-oxide are readily separated by HPLC with fluorometric
detection. This assay proved sensitive enough to monitor FMOs activity in intact
monolayer of cultured hepatocytes. The formation of benzydamine N-oxide was
inhibited when hepatocytes were coincubated with methimazole (another FMO
substrate) in a dose-dependent manner, whereas N-octylamine (an inhibitor of
cytochrome P450) had no inhibitory effect. In contrast to cytochrome P450, FMO
activity assessed by benzydamine N-oxidation was relatively stable for all
species studied during 72-h cultures.

PMID: 10425375 [PubMed - indexed for MEDLINE]