Pharmacokinetic and pharmacodynamic characterization of a novel formulation containing co-formulated interferons alpha-2b and gamma in healthy male volunteers

Abstract

BackgroundMore potent antitumor activity is desired in Interferon (IFN)-treated cancer patients. This could be achieved by combining IFN alpha and IFN gamma. The aim of this work was to characterize the pharmacokinetics and pharmacodynamics of a novel formulation containing a co-formulated combination of IFNs alpha-2b and gamma (CIGB-128-A).MethodsA group of nine healthy male subjects received intramuscularly 24.5 × 106 IU of CIGB-128-A. IFN concentrations were evaluated for 48 h. Serum neopterin, beta2-microglobulin (β2M) and 2′–5′ oligoadenylate synthetase (2′–5′ OAS), classical IFN-inducible serum markers, were measured during 192 h by enzyme immunoassay and body temperature was used as pharmacodynamic variable as well.ResultsConcerning pharmacokinetics, serum IFNs’ profiles were better fitted to a mono-compartmental model with consecutive zero order and first order absorption, one bioavailability value. No interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles. Neopterin and β2M time profiles showed a delay that was efficiently linked to pharmacokinetics by means of a zero order absorption rate constant. Neopterin level was nine-fold higher than initial values, 48 h post-administration, an increment not described before. At this time, mean serum β2M peaked around the double from baseline. Serum concentrations of the enzyme 2′–5′ OAS was still elevated on the 8 day post-injection. The formulation was well tolerated. Most frequent adverse reactions were fever, headache, arthralgia and lymphopenia, mostly mild.ConclusionsThe administration of co-formulated IFN alpha-2b and IFN gamma likely provides improved pharmacodynamic properties that may be beneficial to treat several malignancies.Trial registrationCuban Public Registry of Clinical Trials RPCEC00000118, May 24, 2011.

HeberFERON, a promising choice for the treatment of basal cell carcinoma

“…This result confirmed in vivo the biological potency of this new formulation of IFNs [4]. Another PK/PD study in healthy volunteers with HeberFERON confirmed the precedent data [5].…”

Effects from oral administration of recombinant interferon-alpha on piglet daily care

“…The results showed that the half-life of IFN was faster, reaching a peak in about 3~4 hours (Zhao et al, 2017). In previous study, after the intramuscular injection of 24.5 × 10 6 IU IFN-α2b and IFN-γ complex, serum IFN-α and IFN-γ began to rise at several hours after the treatment, and then declined after reaching the peak in the human body (García-García et al, 2016). In our study, the oral administration (1500 IU per day per piglet) and intramuscular injection (4× 10 6 IU per day per piglet) was compared.…”

The Effects From Oral Administration of Recombinant Interferon-alpha on Piglet Daily Care

“…The results showed that the half-life of IFN was faster, reaching a peak in about 3 ~ 4 hours (Zhao et al, 2017). In previous study, after the intramuscular injection of 24.5 × 10 6 IU IFN-α2b and IFN-γ complex, serum IFN-α and IFN-γ began to rise at several hours after the treatment, and then declined after reaching the peak in the human body (García-García et al, 2016). In our study, the oral administration (1500 IU per day per piglet) and intramuscular injection (4× 10 6 IU per day per piglet) was compared.…”