Abstract:
:A potential cytokine-drug interaction between interleukin 6 (IL-6) and itraconazole (ITZ) was studied using human hepatocytes in primary culture. Cultures from 5 adult males (mean age 42 +/- 15 years) who had not received any medicines known to interact with CYP3A4 were studied. Cultures were exposed to ITZ 500 ng/ml, and the effects of 120 microg/ml cimetidine, 50 ng/ml human IL-6, or IL-6 plus IL-6 receptor antagonist were analyzed for 2, 4, 8, and 12 h. Intracellular ITZ and hydroxyitraconazole concentrations were measured using HPLC and normalized to total cellular protein. Mean intracellular concentrations between groups were compared using one-way Anova (f test; p < 0.10) and corresponding Bonferroni versus control test for multiple comparisons (p < 0.02). Mean intracellular ITZ concentrations between the groups were similar at all time points. Human hepatocytes in primary culture can metabolize ITZ. However, IL-6 did not inhibit hydroxyitraconazole formation, but it may inhibit its subsequent metabolism.
journal_name
Pharmacologyjournal_title
Pharmacologyauthors
Gubbins PO,Melchert RB,McConnell SA,Franks AM,Penzak SR,Gurley BJdoi
10.1159/000068401subject
Has Abstractpub_date
2003-04-01 00:00:00pages
195-201issue
4eissn
0031-7012issn
1423-0313pii
68401journal_volume
67pub_type
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