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Pegylated interferon‐α2b: Pharmacokinetics, pharmacodynamics, safety, and preliminary efficacy data
Author(s) -
Glue Paul,
Fang Jane W.S.,
RouzierPanis Regine,
Raffanel Claude,
Sabo Ron,
Gupta Samir K.,
Salfi Margaret,
Jacobs Sheila
Publication year - 2000
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2000.110973
Subject(s) - pharmacokinetics , medicine , pegylated interferon , pharmacodynamics , interferon , pharmacology , adverse effect , gastroenterology , neopterin , hepatitis c , hepatitis c virus , immunology , virus , ribavirin
Aims The objectives of this study were to assess the safety, pharmacokinetic and pharmacodynamic profiles, and antiviral efficacy of pegylated interferon‐α2b monotherapy in patients with chronic hepatitis C. Methods Fifty‐eight patients (38 men, 20 women; age range, 25 to 65 years) with compensated chronic hepatitis C were enrolled in this open‐label, randomized, active controlled study. Patients received 0.035 to 2.0 μg/kg pegylated interferon‐α2b subcutaneously weekly or the active control, interferon‐α2b 3 million IU subcutaneously three times/week, for 24 weeks. Safety and antiviral efficacy assessments were performed during treatment and in a subsequent 4‐week follow‐up period. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. Results Pegylated interferon‐α2b produced dose‐related reductions in white blood cells, neutrophils, and platelets, and dose‐related increases in oral temperature, serum neopterin, and serum 2′5′‐oligoadenylate synthetase activity, which were qualitatively similar to those produced by nonpegylated interferon‐α2b. Reported adverse events (flu‐like symptoms, asthenia) were qualitatively similar in pegylated interferon‐α2b– and nonpegylated interferon‐α2b–treated groups. Dose‐related antiviral activity, as measured by loss of detectable serum hepatitis C virus RNA (<100 copies/mL), was noted at the end of treatment and after 4 weeks of follow‐up. Both pegylated and nonpegylated interferon‐α2b were rapidly absorbed, with maximal concentrations occurring ~8 to 12 hours after dose administration. Pegylated interferon‐α2b had sustained maximal serum concentrations for 48 to 72 hours after dose administration, whereas nonpegylated interferon‐α2b concentrations declined rapidly. Volume of distribution for both compounds was similar (~1 L/kg). Pegylated interferon‐α2b elimination half‐life was approximately 10‐fold greater, and mean apparent clearance was one tenth that of nonpegylated interferon‐α2b. Conclusions Pegylated and nonpegylated interferon‐α2b safety and pharmacodynamic profiles were comparable. Pegylated interferon‐α2b demonstrated delayed clearance compared with nonpegylated interferon‐α2b, consistent with once‐weekly administration. Clinical Pharmacology & Therapeutics (2000) 68 , 556–567; doi: 10.1067/mcp.2000.110973