Interferon reduces hepatic drug metabolism in vivo in mice.
The effects of two highly purified human leukocyte interferons (IFN-A and IFN-AD) on drug-metabolizing capacity in mice have been investigated. IFN-AD was found to produce significant changes in antipyrine half-life, assessed by analysis of 14CO2 exhalation rates following 14C-antipyrine administration. By contrast, IFN-A, which has considerably less antiviral potency than IFN-AD, was found to have no effect on antipyrine half-life. The administration regimen was found to markedly alter the effects seen with IFN-AD. When IFN-AD was given as single daily doses (5 X 10(7) units/kg/day X 3 days), the half-life of antipyrine increased by a mean of 40% (from 21.0 to 28.9 min). However, when a smaller daily dose (3 X 10(7) units/kg/day) was given as a continuous infusion, the antipyrine half-life increased by more than 3-fold (from 20.8 to 68.5 min) after 3 days of administration. Continued infusion for a further 3 days produced no additional change in antipyrine half-life. These results demonstrate that human leukocyte interferons can significantly inhibit hepatic metabolic activity in vivo.
Taylor
G
G
Marafino
B J
BJ
Moore
J A
JA
Gurley
V
V
Blaschke
T F
TF
D000818:Animals; D000983:Antipyrine / Q000378:metabolism; D001571:Benzoflavones / Q000494:pharmacology; D001944:Breath Tests; D002250:Carbon Radioisotopes; D002927:Cimetidine / Q000494:pharmacology; D006207:Half-Life; D007263:Infusions, Parenteral / Q000295:instrumentation; D007274:Injections, Intraperitoneal; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001571:Benzoflavones; D002250:Carbon Radioisotopes; D007370:Interferon Type I; C011512:alpha-naphthoflavone; D002927:Cimetidine; D006899:Mixed Function Oxygenases; D000983:Antipyrine