Interferon beta-1b

Interferon beta-1b has been shown to possess both antiviral and immunoregulatory activity. The mechanisms by which interferon beta-1b exerts its actions in multiple sclerosis are not clearly understood. However, it is known that the biological response-modifying properties of interferon beta-1b are mediated through its interactions with specific cell receptors found on the surface of human cells. The binding of interferon beta-1b to these receptors induces the expression of a number of gene products that are believed to be the mediators of the biological actions of interferon beta-1b.

A number of these products have been measured in the serum and cellular fractions of blood collected from patients treated with interferon beta-1b. Interferon beta-1b both decreases the binding affinity and enhances the internalisation and degradation of the interferon-gamma receptor. Interferon beta-1b also enhances the suppressor activity of peripheral blood mononuclear cells.

Interferons belong to the family of cytokines, which are naturally occurring proteins. Interferons have molecular weights ranging from 15,000 to 21,000 Daltons. Three major classes of interferons have been identified: alpha, beta, and gamma. Interferon alpha, interferon beta, and interferon gamma have overlapping yet distinct biological activities. The activities of interferon beta-1b are species-restricted and therefore, the most pertinent pharmacological information on interferon beta-1b is derived from studies of human cells in culture or human in vivo studies.

Interferon beta-1b serum levels were followed in patients and volunteers by means of a bioassay that was not completely specific. Maximum serum levels of about 40 IU/ml were found 1-8 hours after subcutaneous injection of 500 microgram (16.0 million IU) interferon beta-1b. From various studies mean clearance rates and half-lives of disposition phases from serum were estimated to be at most 30 ml·min^-1 ·kg^-1 and 5 hours, respectively.

Administration of interferon beta-1b injections every other day does not lead to serum level increase, and the pharmacokinetics do not seem to change during therapy.

The absolute bioavailability of subcutaneously administered interferon beta-1b was approximately 50%.

No acute toxicity studies have been performed. As rodents do not react to human interferon beta, repeated dose studies were carried out with rhesus monkeys. Transitory hyperthermia was observed, as well as a significant rise in lymphocytes and a significant decrease in thrombocytes and segmented neutrophils.

No long-term studies have been conducted. Reproduction studies with rhesus monkeys revealed maternal toxicity and an increased rate of abortion, resulting in prenatal mortality. No malformations have been observed in the surviving animals.

No investigations on fertility have been conducted. No influence on the monkey oestrous cycle has been observed. Experience with other interferons suggest a potential for impairment of male and female fertility.

In one single genotoxicity study (Ames test), no mutagenic effect has been observed. Carcinogenicity studies have not been performed. An in vitro cell transformation test gave no indication of tumorigenic potential.