Interferon 3-la in the Treatment of Multiple Sclerosis: CLINICAL PHARMACOLOGY
Interferons are naturally occurring proteins that demonstrate immuno-modulatory, antiviral, and antiprolifera-tive biological activities. They exert their biological effects by binding to specific receptors on the surface of cells. The binding of interferon beta to its receptors initiates a complex cascade of intra-cellular events that leads to the expression of numerous interferon-induced gene products and markers, including 2′,5′-oligoadenylate synthetase, |32-micro-globulin, and neopterin, which may mediate some of the biological activities. The specific interferon-induced proteins and the mechanisms by which interferon |3-1a exerts its effects in MS have not been fully defined.
In healthy volunteer subjects, a single subcutaneous injection of 60 mcg of inter-feron resulted in a peak serum concentration (Cmax) of 5.1 ± 1.7 International Units (IU)/ml (mean ± SD), with a median time of peak serum concentration (Tmax) of 16 hours. The serum elimination half-life (t1/2) was 69 ± 37 hours, and the area under the serum concentration versus the time curve (AUC), from zero to 96 hours, was 294 ± 81 IU-hours/ml. Following subcutaneous injections in healthy volunteer subjects every other day, an increase of approximately 240% in the AUC was observed, suggesting that accumulation of interferon |3-1a occurs after repeated administration. The total clearance is approximately 33 to 55 liters/hour.
The pharmacokinetic parameters of interferon p-1a in children, geriatric patients, and patients with renal or hepatic insufficiency have not been established. canadian pharmacy online
The most commonly reported adverse reactions after administration of interferon were injection-site disorders; influenza-like symptoms such as headache, fatigue, fevers, rigors, chest pain, back pain, myalgia, and abdominal pain; depression; elevation of liver enzymes; and hematological abnor-malities.
DOSAGE AND ADMINISTRATION
The recommended dosage of inter-feron | -1a is 44 mcg, injected subcuta-neously three times per week. If possible, the drug should be administered at the same time on the same three days (i.e., Monday, Wednesday, Friday) at least 48 hours apart each week. Generally, the dose should be started at 8.8 mcg subcutaneously three times weekly and increased over a four-week period to 44 mcg three times weekly. Leukopenia or elevated liver-function test values may warrant dose reductions of 20% to 50% until toxicity is resolved. cialis professional
The drug is available as a sterile, preservative-free solution in prefilled syringes of 22 mcg and 44 mcg.