Alpha interferon has no effect on lidocaine metabolism in the rat.
Interferons (IFN) inhibit activity of many isoenzymes of the hepatic microsomal cytochrome P-450 system. This inhibition is species specific. Lidocaine is metabolized by cytochrome P-450 III A 4. We investigated in the rat the effect of rat alpha-IFN on lidocaine elimination and on its extraction by the isolated perfused rat liver. To determine elimination, the femoral artery and vein were cannulated. 24 h later, the conscious rat was given lidocaine through the venous catheter and blood was drawn from the arterial catheter for lidocaine determination every 3 min for 20 min. 7 rats were pre-treated with intramuscular rat alpha-IFN 7.5 x 10(5) U, 24 h prior to the experiment and another 4 rats were given saline i.m. The lidocaine elimination rate constant was unchanged, 0.065 min-1 and 0.063 min-1 for the control and IFN groups, respectively. To investigate lidocaine extraction, the isolated perfused rat liver was used. Perfusate samples from the portal and hepatic veins were drawn at 2 min intervals for 20 min, and lidocaine extraction determined. Extraction was determined in two groups of 6 rats each. The first group served as control and these rats were injected with saline only, while in the second group, the rats were pre-treated with rat alpha-IFN 7.5 x 10(5) U. Lidocaine extraction by the isolated perfused rat liver remained unchanged, 97.0 +/- 0.7% and 94.0 +/- 2.4% in the control and IFN treated groups, respectively. It is concluded that the rat alpha-IFN affects neither the elimination nor the extraction of lidocaine.
Melzer
E
E
Department of Gastroenterology, Sheba Medical Center, Tel Hashomer, Israel.
Bardan
E
E
Ronen
I
I
Krepel
Z
Z
Bar Meir
S
S
D000818:Animals; D001835:Body Weight; D004347:Drug Interactions; D006207:Half-Life; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000494:pharmacology*; D008012:Lidocaine / Q000493:pharmacokinetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size; D051381:Rats
D016898:Interferon-alpha; D008012:Lidocaine