title: In vitro metabolism of norbormide in rat, mouse and guinea pig liver preparations.
abstract: Differences between species in response to norbormide (NRB) may arise through differential pharmacodynamic and/or pharmacokinetic properties. We hypothesise that species-selectivity is at least partly determined by differences in metabolism based on in vitro data generated in liver preparations from rats, mice and guinea pigs. HPLC separation and LC/MS identification revealed that NRB undergoes metabolism primarily to hydroxylated form that was tentatively identified in both rat and non-rat species with NADPH as the preferred cofactor. However, the metabolic profile and the rate are different between species. Gender differences are also reported in the metabolic rate in rats and we postulate that this may be responsible for different toxic sensitivities seen between sexes. Using this knowledge, we aim to develop pharmacological tool(s) for use in designing a new class of drugs that can be targeted in a tissue-selective manner. Further in vivo pharmacokinetic with receptor affinity studies are warranted.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, New Zealand; Landcare Research, Private Bag 92170, Auckland 1142, New Zealand.
authors.forename: Shanthinie
authors.initials: S
authors.lastname: Ravindran
authors.forename: Brian
authors.initials: B
authors.lastname: Hopkins
authors.forename: Sergio
authors.initials: S
authors.lastname: Bova
authors.forename: David
authors.initials: D
authors.lastname: Rennison
authors.forename: Margaret
authors.initials: M
authors.lastname: Brimble
authors.forename: Malcolm
authors.initials: M
authors.lastname: Tingle