CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS OF TWO FORMULATIONS CONTAINING SYNERGISTIC PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA IN HEALTHY MALE VOLUNTEERS (SOFIA STUDY)

J Pharm Pharmacogn Res 2(Suppl. 1): S9, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication

CO 017: PHARMACODYNAMICS AND PHARMACOKINETICS OF TWO FORMULATIONS CONTAINING SYNERGISTIC PROPORTIONS OF INTERFERONS ALPHA-2B AND GAMMA IN HEALTHY MALE VOLUNTEERS (SOFIA STUDY)

García I1, Díaz A2, Tuero AD1, González CA2, Pérez S2, García Y1, Campos R1, Valenzuela CM1, Cruz A1, Cervantes M1, Martín A2, Vásquez DM3, Howland I4, Bello I1.

1Clinical Investigation Department, Center for Genetic Engineering and Biotechnology (CIGB), Ave 134 e/ 23 and 25, Cubanacán, Playa, P.O. Box 6332, Havana 10600, Cuba. Telephone: +53 (7) 2087379; 2087465; Fax: +53 (7) 2736008. Email: idrian.garcia@cigb.edu.cu
2National Center for Toxicology, “Carlos J. Finlay” University Hospital, Ave. 31 and 114, Marianao, Havana 11400, Cuba.
3Genomics Department, CIGB, Ave 134 e/ 23 and 25, Cubanacán, Playa, Havana 10600, Cuba.
4Clinical Laboratory, Center for Medical-Surgical Research, 216 and 11-B, Siboney, Playa, Havana 10600, Cuba.
Abstract

Introduction: A sustained full Interferon (IFN)-receptor interactions with more potent antiproliferative activity are desired in the treatment of cancer. This is possible to obtain combining IFN-alpha and IFNgamma that synergize for their biological activities.

The aim of this study was to characterize pharmacodynamics, pharmacokinetics and biological safety of two formulations (CIGB-128 and CIGB-128-A) based on the combination of IFNs alpha-2b and gamma in healthy male volunteers.

Material and methods: A randomized, crossover, double-blind study with a 3-weeks washout period, was done. A single 24.5 x 106 IU IFN mixture dose was administered intramuscularly. Thirteen apparently healthy male subjects were included. Classical IFN-inducible serum markers, neopterin, beta2-microglobulin (β2M), and 2’-5’ oligoadenylate synthetase (2′-5′ OAS), were used as indicators of their pharmacodynamic action. Serum IFN concentration was measured during 48 hours by enzyme immunoassay. Adverse events were rigorously checked.

Results: Neopterin levels at 24-48 hours post-administration were 9 times superior to the initials. This high increment has not been described before in the literature with any subtype or variant of IFN. At the same time mean serum β2M peaked around the double from baseline. The concentrations of the enzyme 2′-5′ OAS were still elevated at the eighth day post-injection. Concerning pharmacokinetics, no interferences by simultaneous administered IFNs were observed in their typical similar systemic profiles; parameters as Tmax (7-10 hours) and t1/2 (6 hours) were within the reported ranges for these conventional IFNs. Both products were well tolerated. The most frequent adverse reactions were fever, headache, arthralgias and lymphopenia, mostly mild. Serum IFN concentrations has a direct, strong correlation with body temperature.

Conclusions: The potent synergistic IFN mixture possesses improved pharmacodynamic properties without additional toxicity that may useful in the oncologic setting leading to less frequent injections, and a better patient’s compliance and quality of life.