Bc. Israel et al., EFFECTS OF INTERFERON-ALPHA MONOTHERAPY ON HEPATIC DRUG-METABOLISM INCANCER-PATIENTS, British journal of clinical pharmacology, 36(3), 1993, pp. 229-235
1 The influence of interferon-alpha (IFNalpha) on the clearances of th
eophylline (TH), antipyrine (AP) and hexobarbitone (HB) was studied in
seven cancer patients given IFNalpha as their only treatment. In addi
tion, IFNalpha effects on drug clearance were correlated with changes
in serum inflammatory cytokines and acute phase proteins. 2 A 'baselin
e' study was performed by administering an oral drug 'cocktail' of TH
(150 mg), AP (250 mg) and HB (250 mg) with saline injected simultaneou
sly and again 24 h later. One week later, an 'acute' study was perform
ed at the initiation of IFNalpha therapy, 3 X 10(6) units injected wit
h the drug cocktail and again 24 h later. After 2 weeks of IFNalpha tr
eatment three times per week, a 'chronic' study was performed with IFN
alpha injected the day prior to, simultaneously with, as well as 24 h
after the drug cocktail. 3 Plasma samples were collected over 48 h and
the clearances of TH, AP and HB were estimated. Serum samples were co
llected at various times for the measurement of tumor necrosis factor
(TNF), interleukin-I (IL-1), interleukin-6 (IL-6), C-reactive protein
(C-RP) and alpha1-acid glycoprotein (AGP). 4 IFNalpha caused a 33% dec
rease in the oral clearance of TH during the chronic study compared wi
th baseline (P less-than-or-equal-to 0.05). Although IFNalpha inhibite
d TH clearance by 16% during the acute study and AP clearance by 20-21
% during both acute and chronic studies, these changes did not reach s
tatistical significance. IFNalpha caused minimal changes in HB clearan
ce. There were no chronic effects of IFNalpha on serum cytokines or ac
ute phase proteins. 5 The findings confirm that the most commonly used
dose of IFNalpha inhibits the hepatic clearance in humans of some but
not all drugs and that this inhibition persists during IFNalpha thera
py. Because inhibition was not associated with increases in serum cyto
kines or acute phase proteins, the mechanism by which IFNalpha inhibit
s cytochrome P450 activities in vivo does not appear to involve inflam
matory mediators such as TNF, IL-1 or IL-6.