Range |
Table - link
|
Organism |
Unspecified |
Reference |
Keizer RJ, Huitema AD, Schellens JH, Beijnen JH. Clinical pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010 Aug49(8):493-507. doi: 10.2165/11531280-000000000-00000. pp.497-8 table IIPubMed ID20608753
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Primary Source |
See refs beneath table |
Method |
P.495 left column bottom paragraph: "mAbs differ from small-molecule drugs not only in their pharmacological mechanism of action but also in their
pharmacokinetic properties. As is presented in this review, the complex but incompletely elucidated distribution and elimination mechanisms of mAbs provide an explanation for the
long elimination half-lives that are generally observed. Insight into these mechanisms is important, both in the development of these drugs and in clinical practice, e.g. in the development and optimization of dosage regimens. In this review, the disposition mechanisms of mAbs are discussed, focusing on clinical
pharmacokinetic characteristics of the currently approved mAbs." |
Comments |
P.499 left column 3rd paragraph: "A second elimination route is degradation within the target cell, which occurs after internalization and subsequent intracellular degradation in lysosomes [refs 70,71]. For mAbs targeting an antigen located on cells, degradation by target cells after binding of the Fv [Fragment variable]-part to the target antigen (‘target-mediated elimination’) is probably a more important elimination route than proteolysis by cells of the RES [Reticuloendothelial System, refs 72-74]. Since this route is saturable because of the finite amounts of the target antigen, for these mAbs, nonlinear elimination has often been reported (table II). This elimination route is also referred to as the ‘antigen sink’. The degradation of efalizumab by T cells expressing CD11a (the target of efalizumab) has been shown to be an important elimination mechanism for this mAb [ref 74]. Internalization effectively removes the antibody from plasma or extracellular fluid, although it may be that intracellular lysosomal degradation is a much slower process [ref 72]." |
Entered by |
Uri M |
ID |
112409 |