Background: More potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be\nachieved by combining IFN alpha and IFN gamma. The aim of this work was to characterize the pharmacokinetics\nand pharmacodynamics of a novel formulation containing a co-formulated combination of IFNs alpha-2b and\ngamma (CIGB-128-A).\nMethods: A group of nine healthy male subjects received intramuscularly 24.5 Ã?â?? 106 IU of CIGB-128-A. IFN\nconcentrations were evaluated for 48 h. Serum neopterin, beta2-microglobulin (Ã?²2M) and 2ââ?¬Â²Ã¢â?¬â??5ââ?¬Â² oligoadenylate\nsynthetase (2ââ?¬Â²Ã¢â?¬â??5ââ?¬Â² OAS), classical IFN-inducible serum markers, were measured during 192 h by enzyme\nimmunoassay and body temperature was used as pharmacodynamic variable as well.\nResults: Concerning pharmacokinetics, serum IFNsââ?¬â?¢ profiles were better fitted to a mono-compartmental model\nwith consecutive zero order and first order absorption, one bioavailability value. No interferences by simultaneous\nadministered IFNs were observed in their typical similar systemic profiles. Neopterin and Ã?²2M time profiles showed\na delay that was efficiently linked to pharmacokinetics by means of a zero order absorption rate constant. Neopterin\nlevel was nine-fold higher than initial values, 48 h post-administration, an increment not described before. At this time,\nmean serum Ã?²2M peaked around the double from baseline. Serum concentrations of the enzyme 2ââ?¬Â²Ã¢â?¬â??5ââ?¬Â² OAS was still\nelevated on the 8 day post-injection. The formulation was well tolerated. Most frequent adverse reactions were fever,\nheadache, arthralgia and lymphopenia, mostly mild.\nConclusions: The administration of co-formulated IFN alpha-2b and IFN gamma likely provides improved\npharmacodynamic properties that may be beneficial to treat several malignancies.
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