Background: Interferon (IFN) alpha conjugation to polyethylene glycol (PEG) results in a better pharmacokinetic\nprofile and efficacy. The aim of this study was to compare the pharmacokinetic, pharmacodynamic and safety\nproperties of a new, locally developed, 40-kDa PEG-IFN alpha-2b preparation with a reference, commercially\navailable PEG-IFN alpha-2a in healthy male volunteers.\nMethods: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 180\nmicrograms PEG-IFN alpha-2 dose was administered subcutaneously in both groups. Sixteen apparently healthy\nmale subjects were included. Serum PEG-IFN concentration was measured during 336 hours by an enzyme\nimmunoassay (EIA). Other clinical and laboratory variables were used as pharmacodynamic and safety criteria.\nResults: The pharmacokinetic comparison by EIA yielded a high similitude between the formulations. In spite of a\nhigh subject variability, the parameters� mean were very close (in all cases p > 0.05): AUC: 53623 vs. 44311 pg.h/mL;\nCmax: 333 vs. 271 pg/mL; Tmax: 54 vs. 55 h; half-life (t1/2): 72.4 vs. 64.8 h; terminal elimination rate (lambda): 0.011\nvs. 0.014 h-1; mean residence time (MRT): 135 vs. 123 h for reference and study preparations, respectively. There\nwere no significant differences with respect to the pharmacodynamic variables either: serum neopterin and beta-2\nmicroglobulin levels, stimulation of 2�5� oligoadenylate synthetase expression, and serum IFN antiviral activity. A\nstrong Spearman�s rank order correlation (p < 0.01) between the pharmacokinetic and pharmacodynamic\nconcentration-time curves was observed. Both products caused similar leukocyte counts diminution and had similar\nsafety profiles. The most frequent adverse reactions were leukopenia, fever, thrombocytopenia, transaminases\nincrease and asthenia, mostly mild.\nConclusions: Both formulations are fully comparable from the pharmacokinetic, pharmacodynamic, and safety\nprofiles. Efficacy trials can be carried out to confirm clinical similarity.
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