: 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.
Recombinant tumor necrosis factor reduces hepatic drug metabolism in vivo in the rat
Ghezzi, P;Conti, I;
1988
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
