Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C
| Autor: | Karen Kolz, Samir K. Gupta, David L. Cutler |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Time Factors Amino-Acid N-Acetyltransferase Hepacivirus Interferon alpha-2 Dapsone Pharmacology Biology Antiviral Agents Polyethylene Glycols Cytochrome P-450 CYP2C8 Young Adult Tolbutamide Pharmacokinetics Cytochrome P-450 CYP1A2 Pegylated interferon Internal medicine medicine Cytochrome P-450 CYP3A Humans Pharmacology (medical) Adverse effect CYP2C8 Interferon-alpha Biological activity General Medicine Hepatitis C Chronic Middle Aged Recombinant Proteins Endocrinology Cytochrome P-450 CYP2D6 Inactivation Metabolic Toxicity Female Aryl Hydrocarbon Hydroxylases medicine.drug |
| Zdroj: | European Journal of Clinical Pharmacology. 67:591-599 |
| ISSN: | 1432-1041 0031-6970 |
| Popis: | To examine the effect of pegylated interferon (PEG-IFN) alfa-2b on the activity of major drug-metabolizing enzymes. 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 μg/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. 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/m2. 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. Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals. |
| Databáze: | OpenAIRE |
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