Antibodies Half life

A typical kinetic profile is divided into alpha and beta phases. The alpha phase occurs rapidly (in the first 24 h) and is considered to be the period in which the administered antibody reaches equilibrium. The beta phase then continues for several days in a direct log-linear relationship of serum concentration to time. It is this beta phase that is considered to be the most reliable indicator of antibody half-life in circulation. To establish beta phase kinetics, we take blood samples (25-75 xl depending on the frequency of sampling) at 1-4 days following administration, followed by... 

Category Immunosuppressant Monoclonal antibody Half-life 12 days... 

Indications Metastatic colorectal cancer Category Antineoplastic Monoclonal antibody Half-life 75-188 hours... 

Indications Paroxysmal nocturnal hemoglobinuria (PNH) Category Monoclonal antibody Half-life 272 Hours... 

Indications Reversal of acute allograft rejection in renal, cardiac and hepatic transplant patients Category Immunosuppressant Monoclonal antibody Half-life N/A... 

Indications Prophylaxis of serious lower respiratory tract disease caused by RSV in pediatric patients Category Immunomodulator Monoclonal antibody Half-life 18 days... 

Indications Wet, age-related macular degeneration Category Recombinant humanized monoclonal antibody Half-life 9 days... 

Indications Non-Hodgkin s lymphoma Category Immunosuppressant Monoclonal antibody Half-life 60 hours (after first infusion)... 

Category Anti-interleukin-6 receptor monoclonal antibody Half-life N/A... 

Trade names Bexxar (Corixa) (GSK) Iodine131 l-Tositumomab (MDS Nordion) Tositumomab Indications Non-Hodgkin lymphoma Category Antineoplastic Monoclonal antibody Half-life 8.04 days... 

In macromolecular dmg delivery systems, dmgs are attached to polymeric compounds, such as synthetic polymers [60], dendrimers [61], and antibodies [62], in order to enhance the delivery of the active substance to the diseased tissue and to reduce the toxicity to healthy tissue. The use of macromolecular delivery systems provides several advantages extension of the half-life of the dmg, the ability to introduce targeting moieties into the carrier, the possibility of triggered dmg release, and the aforementioned reduced cytotoxicity. 

Kennedy et al. developed a lasalocid immunoassay for application to residues in chicken meat and liver samples. The antibody was specific and did not cross-react with salinomycin, maduramicin, or monensin. Sample preparation consisted of homogenization in aqueous acetonitrile, removal of fat from an aliquot of the aqueous acetonitrile by hexane extraction, and evaporation of acetonitrile. The sample was then reconstituted with assay buffer. Liver required an additional solid phase extraction step. The LOQ was 0.02 xgkg for muscle and 0.15 agkg for liver. These workers were able to use the system to determine the half-life of lasalocid in the tissues. 

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

The prototype of this class is hirudin, which was originally isolated from the salivary glands of the medicinal leech, Hirudo medicinalis. Hirudin itself is not commercially available, but recombinant technology has permitted production of hirudin derivatives, namely lepirudin and desirudin.29,38,41 Lepirudin has a short half-life of approximately 40 minutes after IV administration and 120 minutes when given SC. Elimination of lepirudin is primarily renal therefore, doses must be adjusted based on the patient s renal function. The dose should be monitored and adjusted to achieve an aPTT ratio of 1.5 to 2.5 times the baseline measurement. Lepirudin is currently approved for use in patients with HIT and related thrombosis. Up to 40% of patients treated with lepirudin will develop antibodies to the drug.29,38,41... 

Alemtuzumab is the antibody to the CD52 receptor present on B and T lymphocytes. The pharmacokinetics of alemtuzumab demonstrate a terminal half-life of 7 days. Alemtuzumab has shown clinical activity in the treatment of chronic lymphocytic leukemia. Severe and prolonged (6 months) immunosuppression may result, which necessitates prophylaxis with cotrimox-azole and antivirals to prevent opportunistic infections. 

Cetuximab is a human/mouse antibody that binds to the epidermal growth factor receptor to block its stimulation. The pharmacokinetics of cetuximab demonstrate a volume of distribution that approximates the vascular space and a terminal half-life of 70 to 100 hours. Cetuximab has shown clinical activity in the treatment of colorectal cancer. An acnelike rash may appear on the face and upper torso 1 to 3 weeks after the start of therapy. Other side effects include hypersensitivity reactions, interstitial lung disease, fever, malaise, diarrhea, abdominal pain, and nausea and vomiting. 

Rituximab is a monoclonal antibody to the CD20 receptor expressed on the surface of B lymphocytes the presence of the antibody is determined during flow cytometry of the tumor cells. Cell death results from antibody-dependent cellular cytotoxicity. The pharmacokinetics of rituximab are best described by a two-compartment model, with a terminal half-life of 76 hours after the first infusion and a terminal half-life of 205 hours after the fourth dose.36 Rituximab has shown clinical activity in the treatment of B-cell lymphomas that are CD20+. Side effects include hypersensitivity reactions, hypotension, fevers, chills, rash, headache, and mild nausea and vomiting. 

Although the affinity was decreased fivefold upon PEGylation, PEGylated antibody fragments showed an 8.5-fold higher accumulation in tumors than unmodified antibody fragments, because of a longer serum half-life [46]. 

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