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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/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.
Weekly administration of PEG-IFN alfa-2b to subjects with chronic hepatitis C increased CYP2C8/9 and CYP2D6 activity in some individuals.
Schering-Plough Research Institute, K15-22745 2015 Galloping Hill Road, Kenilworth, NJ, 07033, USA, firstname.lastname@example.org.
This article was published in the following journal.
Name: European journal of clinical pharmacology
To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D.
No long-term data have been published on the durability of response following pegylated interferon (PegIFN) treatment in children with chronic hepatitis C (CHC). This prospective, multi-center, long-t...
Background. Patients treated with interferon (IFN) based therapies may develop exacerbation of autoimmune disease. We herein present the case of a 53-year-old female patient who developed celiac disea...
Peginterferon alfa (alfa) increases the risk of autoimmune disease. Peginterferon lambda-1a (Lambda) acts through a receptor with a more liver-specific distribution compared to the alfa receptor. In a...
Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per w...
This study will assess the safety of Pegylated Interferon Alfa-2b (PEG-IFN) as an adjuvant treatment for melanoma.
The purpose of this study is to determine if 24 weeks of treatment with Pegylated Interferon Lambda plus Ribavirin and 12 weeks of treatment with Pegylated Interferon Lambda plus Ribavirin...
Recombinant interferon (IFN) may be useful in the treatment of HIV. However, the high doses of IFN necessary to keep HIV under control limit its use due to toxic side effects. The purpose ...
Combination Therapy With Pegylated Interferon and Ribavirin in Patients With Chronic Hepatitis C Genotype 2 or 3 Infection Who Previously Have Relapsed After Therapy With Pegylated Interferon and Ribavirin
To evaluate the efficacy of pegylated interferon alfa-2a 40 kD (PEGASYS) combination therapy with ribavirin (Copegus)given for 24 or 48 weeks in patients with chronic hepatitis C (CHC) vir...
A recombinant alfa interferon consisting of 165 amino acids with arginine at positions 23 and 34. It is used extensively as an antiviral and antineoplastic agent.
A recombinant alfa interferon consisting of 165 amino acids with lysine at position 23 and histidine at position 34. It is used extensively as an antiviral and antineoplastic agent.
A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent.
Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL.
Specific molecular sites or structures on or in cells with which interferons react or to which they bind in order to modify the function of the cells. Interferons exert their pleiotropic effects through two different receptors. alpha- and beta-interferon crossreact with common receptors, while gamma-interferon initiates its biological effects through its own specific receptor system.
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...