Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 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 is a selective immunomodulating, antipsoriatic drug that blocks the LFA-3/CD2 interaction necessary for the activation and proliferation of memory effector T cells by binding to CD2 expressed on the T cell surface. Because the CD4+ count is reduced by alefacept, it is recommended that this count be monitored on a regular basis to ensure that it does not drop below 250 cells/mul. Few side effects have been related to the use of alefacept that differ from placebo even when CD4+ counts drop below 250 cells/microl. The side effects that have been reported are minor and include: headache, nasopharyngitis, rhinitis, influenza, upper respiratory tract infections, pruritus, arthralgias, fatigue, nausea, accidental injury and increases in liver enzymes. Serious infections and malignancies do not appear linked to the use of alefacept. The percentage of patients who developed antibodies against alefacept is very low. Alefacept is a very safe biological therapy for moderate-to-severe chronic plaque psoriasis with few side effects reported. The utility of checking CD4 counts while administering alefacept for 12 weeks appears minimal.
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PMID:Alefacept: a safety profile. 1625 57