title: Recombinant tumor necrosis factor reduces hepatic drug metabolism in vivo in the rat.
abstract: To verify the potential in vivo inhibitory effect on liver function of tumor necrosis factor (TNF), also known as cachectin, antipyrine and diazepam were chosen to probe the hepatic mixed-function oxidase system. A single dose of TNF (30 micrograms/kg) to rats significantly reduced the plasma clearance of antipyrine and diazepam by about 30% and 25%, respectively; this resulted in concomitant prolongation of the elimination half-life (t1/2) of the two drugs, although of borderline significance for the benzodiazepine. This was probably due to a decrease in hepatic cytochrome P-450 activities that are responsible for antipyrine and diazepam metabolism in TNF-treated rats. This could be of clinical relevance if a similar effect occurs in humans after therapeutically effective doses of this biological response modifier.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Duan
authors.forename: P
authors.initials: P
authors.lastname: Ghezzi
authors.forename: I
authors.initials: I
authors.lastname: Conti
authors.forename: R
authors.initials: R
authors.lastname: Tridico
authors.forename: M
authors.initials: M
authors.lastname: Bianchi
authors.forename: S
authors.initials: S
authors.lastname: Caccia
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003975:Diazepam; D000983:Antipyrine