Assessment of the safety, tolerability, and PK/PD properties of two new formulations of subcutaneously administered IFN-?1a: a double-blind, placebo-controlled comparison with the currently available formulation

Pharmacokinetic considerations in the treatment of multiple sclerosis with interferon-β

“…Indeed, RNF shows a significantly lower neutralizing ADA frequency (at week 96: 17 vs 24%) but it seems that RNF causes a higher rate of FLS (at week 96: 68 vs 38%) [95]. This might be due to higher mean C max values induced by RNF as compared to the original formulation of Rebif (19.9 vs 12.8 IU/ml), even though this study did not calculate the level of significance [36].…”

“…These adverse events manifest usually 3 --6 h after (SC or IM) injection of IFNb and constantly improve within 24 h [94]. Based on the temporal evolution of FLS one might hypothesize that there is an association with IFNb levels, as after SC or IM administration IFNb serum concentrations peak mostly after a mean time of 3 --4 h [25][26][27][28]35] up to a maximum of 18 h [29,30,[32][33][34]37], with a half-life of usually up to 1 day [29,30,36]. Of note, some human PK studies used antiviral activity as a surrogate marker for IFNb concentrations and are therefore, strictly spoken, not true PK investigations (see chapter 9).…”

“…Eventually, IM and SC administration of IFNb exhibit protracted absorption, which results in peak plasma concentrations after several hours [25][26][27][28][29][32][33][34][35][36][37]. IFNb concentrations are detectable for~1 --2 days after injection and, therefore, for a longer time period than after intravenous (IV) administration [25,29,32,33,37].…”

“…Whereas IFNb serum levels peak early after administration (within minutes after IV [26][27][28] and several hours after SC or IM injection [25][26][27][28][29][32][33][34][35][36][37]), the classical PD markers (see above) peak after approximately 24 h [26][27][28][29]35] up to 48 h [34,36,37]. With continuous therapy, there are also late IFNb effects, as for example MMP-9 concentrations are significantly decreased (as compared to baseline) not before a treatment period of several months [49,85].…”

Recombinant interferon-alpha2b poly(lactic-co-glycolic acid) microspheres: pharmacokinetics-pharmacodynamics study in rhesus monkeys following intramuscular administration

“…Neopterin is the marker of IFN activity in primate animals. It has been used to study IFN-γ [10,11] and IFN-β and IFN-α [12,13] . Since the neopterin production of monocyte-macrophages induced by IFN-α is far below that induced by IFN-γ, based on the pharmacodynamic research method for PEG-IFN-β [14] , the dosage adopted in this study was relatively high.…”