Tissue distribution of 35S-metabolically labeled neublastin (BG00010) in rats. 2020

Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
Biogen, Cambridge, MA 02142, United States. Electronic address: natasha.penner@biogen.com.

Neublastin (NBN) is a neurotrophic growth factor that promotes the survival and regenerative properties of nociceptive neurons and has been tested in clinical trials as a treatment for neuropathic pain in individuals with sciatica and painful lumbosacral radiculopathy. Like many low molecular weight heparin binding proteins, NBN is rapidly cleared from the blood following systemic administration. To explore ADME properties of NBN in rats, we used metabolically 35S-labeled NBN following IV and SC administration quantifying counts and intact protein in kidney, liver, brain, serum, and urine at 5 min, 8 h, 24 h and 48 h, and biodistribution in whole body carcasses by QWBA at 2, 8, 48, 96, and 168 h post dose. NBN is rapidly taken up by tissues mainly by liver and kidney and then degraded. Products of degradation are excreted in urine or recycled and utilized for resynthesis. The data we generated for NBN provides a first look at the complex clearance mechanisms for this protein and should aid in the design of ADME studies for other heparin binding proteins.

UI MeSH Term Description Entries
D008297 Male Males
D009414 Nerve Growth Factors Factors which enhance the growth potentialities of sensory and sympathetic nerve cells. Neurite Outgrowth Factor,Neurite Outgrowth Factors,Neuronal Growth-Associated Protein,Neuronotrophic Factor,Neurotrophic Factor,Neurotrophic Factors,Neurotrophin,Neurotrophins,Growth-Associated Proteins, Neuronal,Neuronal Growth-Associated Proteins,Neuronotrophic Factors,Neurotrophic Protein,Neurotrophic Proteins,Proteins, Neuronal Growth-Associated,Factor, Neurite Outgrowth,Factor, Neuronotrophic,Factor, Neurotrophic,Factors, Nerve Growth,Factors, Neurite Outgrowth,Factors, Neuronotrophic,Factors, Neurotrophic,Growth Associated Proteins, Neuronal,Growth-Associated Protein, Neuronal,Neuronal Growth Associated Protein,Neuronal Growth Associated Proteins,Outgrowth Factor, Neurite,Outgrowth Factors, Neurite,Protein, Neuronal Growth-Associated
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D006493 Heparin A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013460 Sulfur Isotopes Stable sulfur atoms that have the same atomic number as the element sulfur, but differ in atomic weight. S-33, 34, and 36 are stable sulfur isotopes. Isotopes, Sulfur
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
January 1973, Naunyn-Schmiedeberg's archives of pharmacology,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
January 1987, Drug metabolism and disposition: the biological fate of chemicals,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
April 1989, Analytical biochemistry,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
January 1985, Xenobiotica; the fate of foreign compounds in biological systems,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
March 1964, Japanese journal of microbiology,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
April 2001, Methods (San Diego, Calif.),
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
December 1972, Journal of pharmaceutical sciences,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
January 1969, The Italian journal of biochemistry,
Natalia Penner, and Shobha Purushothama, and Blake Pepinsky
July 1969, Chemical & pharmaceutical bulletin,
Copied contents to your clipboard!