Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031350 (pharyngitis)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alefacept, human LFA-3/IgG1 fusion protein, is currently under clinical development for the treatment of chronic plaque psoriasis and other T cell mediated disorders. This recombinant protein binds CD2 on T cells and Fc gamma RIII on accessory cells (e.g., natural killer cells, macrophages), inhibiting T cell activation/proliferation and inducing selective T cell apoptosis. These effects are associated with selective reductions in memory-effector (CD4+ CD45RO+ and CD8+ CD45RO+) T cells. Two open-label studies were conducted in healthy male volunteers to evaluate the pharmacokinetics, biologic activity, and tolerability of a single dose of alefacept when administered as a 0.15 mg/kg 30-sec i.v. bolus (n = 12), 0.04 mg/kg intramuscular (i.m.) injection (n = 8), or 0.04 mg/kg 30-min intravenous (i.v.) infusion (n = 8). i.v. infusion produced a higher Cmax (0.96 +/- 0.26 mcg/ml vs. 0.36 +/- 0.19 mcg/ml) and a shorter Tmax (2.8 +/- 1.9 hr vs. 86 +/- 60 hr) when compared to i.m. injection. Based on AUC0-last and AUC0-infenity values, the relative bioavailability of i.m. to i.v. infusion was approximately 60%. After absorption from the i.m. injection was complete, the rate of alefacept elimination from the serum appeared consistent with the i.v. infusion half-life (approximately 12 days). Biologic activity was demonstrated by transient reductions in absolute number of CD2+ lymphocytes, with notable specificity for memory T-cell subsets. Alefacept was well tolerated; the most common adverse effects were headache, pharyngitis, rash, and myalgia. IM administration was not associated with significant local reactions. Results of these studies support i.v. bolus or i.m. administration of alefacept. An i.m. dose of approximately 150 to 200% of the i.v. dose is an appropriate and convenient alternative to i.v. administration.
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PMID:Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. 1279 39

Alefacept belongs to the new generation of drugs applied in the treatment of psoriasis. It is an immunomodulatory recombinant, fully human lymphocyte function associated antigen-3/immunoglobulin G1 fusion protein (LFA-3-Ig) CD2 antagonist that targets memory-effector T cells by binding CD2 on the T cell surface. It blocks the interactions of leukocyte functional antigen (LFA)-3 with CD2 interaction. This drug is used to treat moderate-to-severe chronic plaque psoriasis and there was conducted a pilot study of psoriatic arthritis. It was observed that Alefacept had reduced peripheral-blood memory effector T-lymphocyte (CD45RO+) counts, cells which are responsible for sustaining the disease. Pharyngitis, dizziness, increased cough, nausea, pruritus, myalgia, chills, injection site inflammation, and accidental injury were recorded. So far, in the conducted trials no generalised immunosuppression or increased risk of infection or malignancy were observed. The possibility of increased risk of infections and malignancies must be considered because of reduced lymphocyte counts.
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PMID:Possibilities of using alefacept in the treatment of psoriasis. 1532 11