Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C.

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Gupta SK, Kolz K, Cutler DL

Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C.

Eur J Clin Pharmacol. 2011 Jun;67(6):591-9. doi: 10.1007/s00228-010-0972-5. Epub 2010 Dec 16.

PubMed ID

21161196 [ View in PubMed

]

Abstract

PURPOSE: To examine the effect of pegylated interferon (PEG-IFN) alfa-2b on the activity of major drug-metabolizing enzymes. METHODS: This nonrandomized, open-label, multiple-dose study examined the effects of PEG-IFN alfa-2b on the activity of CYP450 1A2, 2 C8/9, 2D6, and 3A4 enzymes and N-acetyltransferase in subjects with chronic hepatitis C. Eligible subjects received PEG-IFN alfa-2b 1.5 mug/kg subcutaneously once weekly for 4 weeks (days 3, 10, 17, and 24). Oral probe substrates (dextromethorphan hydrobromide 45 mg, caffeine 200 mg, tolbutamide 500 mg, and dapsone 100 mg) were administered after a 10-h fast on days 1 and 25. Midazolam 4 mg was administered orally on days 2 and 26. Enzyme activity for each CYP450 isozyme and for N-acetyltransferase was estimated based on the ratios of the observed concentrations of the substrates and metabolites in plasma or urine samples. RESULTS: Twenty-six subjects enrolled in the study. Mean age was 44.3 years, mean weight was 78.9 kg, and mean body mass index was 26.3 kg/m(2). Multiple doses of PEG-IFN alfa-2b inhibited CYP1A2 activity to a limited extent (point estimate = 84.2%, 90% confidence interval [CI] 79-90), increased CYP2C8/9 activity to a limited extent (point estimate = 127.6%, 90% CI 115-142), increased CYP2D6 activity (point estimate = 167%, 90% CI 125-223), and had no effect on the activity of CYP3A4 or N-acetyltransferase. CONCLUSION: Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Peginterferon alfa-2b	Cytochrome P450 1A2	Protein	Humans	Unknown	Inhibitor	Details

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">

Drugs	Interaction
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Acenocoumarol Peginterferon alfa-2b	The serum concentration of Acenocoumarol can be increased when it is combined with Peginterferon alfa-2b.
Acetaminophen Peginterferon alfa-2b	The serum concentration of Acetaminophen can be increased when it is combined with Peginterferon alfa-2b.
Acyclovir Peginterferon alfa-2b	The serum concentration of Acyclovir can be increased when it is combined with Peginterferon alfa-2b.
Agomelatine Peginterferon alfa-2b	The serum concentration of Agomelatine can be increased when it is combined with Peginterferon alfa-2b.
Albendazole Peginterferon alfa-2b	The serum concentration of Albendazole can be increased when it is combined with Peginterferon alfa-2b.