Disease relevance of Nirvanol

• An 8-fold increase in fetal resorptions and a significant 11% decrease in fetal body weight was observed in the group treated with l-nirvanol, whereas no or minimal toxicity was observed in the other treatment groups [1].
• ESR studies of molecular interactions of copper(II) nirvanol and copper(II) diisopropylsalicylate with Ehrlich ascites tumor cells [2].

High impact information on Nirvanol

• In conclusion, the highly specific MAb 49-10-20 was used to provide further confirmation that S-mephenytoin N-demethylation to nirvanol is a CYP2B6 selective probe [3].
• The relationships between nirvanol formation and CYP3A levels or activity were found to depend on two HLM samples [3].
• Pharmacodynamics of cytochrome P450 2B induction by phenobarbital, 5-ethyl-5-phenylhydantoin, and 5-ethyl-5-phenyloxazolidinedione in the male rat liver or in cultured rat hepatocytes [4].
• PB and two structural analogues (ethylphenylhydantoin and barbital) induced a variety of drug-metabolizing enzymes (CYP2B, CYP3A, CYP2A, epoxide hydrolase) in a series of inbred strains of rats [5].
• Aromatic hydroxylation of 5-phenyl-5-ethylhydantoin (PEH) has been investigated in humans [6].

Biological context of Nirvanol

• Stereoselective metabolism, pharmacokinetics and biliary elimination of phenylethylhydantoin (Nirvanol) in the dog [7].
• Family studies suggested that poor metabolizer phenotypes of nirvanol and mephenytoin were most likely to have the homozygous genotype for an autosomal recessive allele of deficient aromatic drug hydroxylation [8].

Anatomical context of Nirvanol

• S-Mephenytoin (200 microM) was incubated with human liver microsomes, and nirvanol formation was quantitated by reversed-phase HPLC [9].

Associations of Nirvanol with other chemical compounds

• Equimolar doses of the d- or l-isomers of mephenytoin or nirvanol were administered to pregnant Swiss ICR mice i.p. on gestational day 10 [1].
• Bupropion hydroxylation activity at 250 microM was highly correlated with S-mephenytoin N-demethylation activity (yielding nirvanol), another CYP2B6-mediated reaction, in a panel of 32 human livers (r = 0.94) [10].
• Complexes of the general formula Cu(hyd)2(py)2, where hyd = phenytoin or nirvanol; and py = pyridine were prepared and characterized by infrared and ESR [11].

Gene context of Nirvanol

• Therefore, the N-demethylation of (S)-MP to nirvanol may be a useful means of probing the activity of CYP2B6 in vitro when concentrations of >1000 microM are used, but it is unlikely to be a suitable phenotyping tool for this isoform in vivo, where concentrations of >1000 microM are rarely encountered [12].
• Of the recombinant P450 isoforms tested, only CYP2B6 and CYP2C9 formed nirvanol from (S)-MP [12].
• We tested the ability of human liver microsomes (HLMs) and recombinant human cytochrome P450 (CYP or P450) isoforms to catalyze the N-demethylation of nirvanol-free (S)-mephenytoin [(S)-MP] in vitro [12].

Analytical, diagnostic and therapeutic context of Nirvanol

• Brain and plasma levels of mephenytoin and Nirvanol were determined by gas-liquid chromatography after ip administration of 40 mg of mephenytoin per kg [13].
• Simultaneous enantiospecific separation and quantitation of mephenytoin and its metabolites nirvanol and 4'-hydroxymephenytoin in human plasma by liquid chromatography [14].

References