Each mL also contains 7.5 mg sodium chloride, 1.8 mg sodium phosphate dibasic, 1.3 mg sodium phosphate monobasic, 0.1 mg edetate disodium, 0.1 mg polysorbate 80, and 1.5 mg m-cresol as a preservative.
†
Based on the specific activity of approximately 2.6 × 108 IU/mg protein as measured by HPLC assay.
3MIU 22.5 3 MIU/0.2ml 0.087 SC
5 MIU 37.5 5 MIU/0.2ml 0.144 SC
10 MIU 75 10 MIU/0.2ml 0.288 SC
These packages do not require reconstitution prior to administration (see DOSAGE AND ADMINISTRATION). INTRON A Solution for Injection is a clear, colorless solution.
CLINICAL PHARMACOLOGY
General
The interferons are a family of naturally occurring small proteins and glycoproteins with molecular weights of approximately 15,000 to 27,600 daltons produced and secreted by cells in response to viral infections and to synthetic or biological inducers.
Preclinical Pharmacology
Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Once bound to the cell membrane, interferons initiate a complex sequence of intracellular events. In vitro studies demonstrated that these include the induction of certain enzymes, suppression of cell proliferation, immunomodulating activities such as enhancement of the phagocytic activity of macrophages and augmentation of the specific cytotoxicity of lymphocytes for target cells, and inhibition of virus replication in virus-infected cells.
In a study using human hepatoblastoma cell line HB 611, the in vitro antiviral activity of alpha interferon was demonstrated by its inhibition of hepatitis B virus (HBV) replication.
The correlation between these in vitro data and the clinical results is unknown. Any of these activities might contribute to interferon's therapeutic effects.
Pharmacokinetics
The pharmacokinetics of INTRON® A were studied in 12 healthy male volunteers following single doses of 5 million IU/m2 administered intramuscularly, subcutaneously, and as a 30 minute intravenous infusion in a crossover design.
The mean serum INTRON A concentrations following intramuscular and subcutaneous injections were comparable. The maximum serum concentrations obtained via these routes were approximately 18 to 116 IU/mL and occurred 3 to 12 hours after administration. The elimination half-life of INTRON A following both intramuscular and subcutaneous injections was approximately 2 to 3 hours. Serum concentrations were undetectable by 16 hours after the injections.
After intravenous administration, serum INTRON A concentrations peaked (135–273 IU/mL) by the end of the 30-minute infusion, then declined at a slightly more rapid rate than after intramuscular or subcutaneous drug administration, becoming undetectable 4 hours after the infusion. The elimination half-life was approximately 2 hours.
Urine INTRON A concentrations following a single dose (5 million IU/m2) were not detectable after any of the parenteral routes of administration. This result was expected since preliminary studies with isolated and perfused rabbit kidneys have shown that the kidney may be the main site of interferon catabolism.
There are no pharmacokinetic data available for the intralesional route of administration.
Serum Neutralizing Antibodies
In INTRON A-treated patients tested for antibody activity in clinical trials, serum anti-interferon neutral
