Metabolic fate of KRN8601: Plasma level, distribution, metabolism and excretion of 125I-KRN8601 after a single intravenous administration to rats.

Misaizu, Tadashi; Shinkai, Hiroshi; Tanaka, Hideji; Tanimoto, Masumi; Takahashi, Hideaki; Kikuchi, Kazuko; Tokiwa, Tomonobu

doi:10.2133/dmpk.5.283

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…In the present study, intensive exercise also stimulated the secretion of G-CSF, although the origin of G-CSF was not clear. We found that urine G-CSF levels increased at Post 1 h. G-CSF is metabolized and resolved by several organs but mostly excreted in urine (16). Therefore, this increase of urine G-CSF levels at Post 1 h might reflect the increased levels of G-CSF plasma at Post.…”

Section: Discussionmentioning

confidence: 70%

Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation

Yamada

Kudo

Totsuka

et al. 2002

Journal of Applied Physiology

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We examined the hypothesis that the short, intensive exercise-induced increase in circulating neutrophil counts is affected by the interaction between the endocrine and immune systems. Twelve male winter-sports athletes underwent a maximal exercise test on a treadmill. Blood samples were collected before, immediately after (Post), and 1 h (Post 1 h) and 2 h (Post 2 h) after the exercise. The neutrophil counts increased significantly at Post 1 h ( P < 0.05) and remained significantly high even at Post 2 h ( P < 0.05), showing a leftward shift. Plasma granulocyte colony-stimulating factor (G-CSF) increased at Post ( P < 0.05), and interleukin-6 (IL-6) increased at Post 1 h ( P < 0.05). Plasma G-CSF at Post significantly correlated with the numbers of both neutrophils and stab cells at Post 1 h ( P < 0.05). Plasma IL-6 at Post 1 h levels also correlated significantly with the number of neutrophils at Post 2 h ( P < 0.05). The increase in the levels of plasma G-CSF and IL-6 after intensive exercise may play a role in the mobilization of neutrophils into the circulatory system.

show abstract

Section: Discussionmentioning

confidence: 70%

Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation

Yamada

Kudo

Totsuka

et al. 2002

Journal of Applied Physiology

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show abstract

“…They can be administered intravenously, intramuscularly, or subcutaneously. Drugs with a molecular weight of 5000 or more administered subcutaneously or intramuscularly tend to be absorbed via the lymphatic system, especially in drugs with a molecular weight of 20,000 or more, such as hematopoietic factor preparations [4], erythropoietin [5], and granulocyte colony-stimulating factor [6]. However, because of the extremely slow lymphatic flow rate, it takes time for drugs to reach the systemic circulation.…”

Section: Absorptionmentioning

confidence: 99%

Pharmacokinetics of Biopharmaceuticals: Their Critical Role in Molecular Design

2023

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Biopharmaceuticals have developed rapidly in recent years due to the remarkable progress in gene recombination and cell culture technologies. Since the basic structure of biopharmaceuticals can be designed and modified, it is possible to control the duration of action and target specific tissues and cells by kinetic modification. Amino acid sequence modifications, albumin fusion proteins, polyethylene glycol (PEG) modifications, and fatty acid modifications have been utilized to modify the duration of action control and targeting. This review first describes the position of biopharmaceuticals, and then the kinetics (absorption, distribution, metabolism, elimination, and pharmacokinetics) of classical biopharmaceuticals and methods of drug quantification. The kinetic innovations of biopharmaceuticals are outlined, including insulin analog, antibody-related drugs (monoclonal antibodies, Fab analogs, Fc analogs, Fab-PEG conjugated proteins, antibody-drug conjugates, etc.), blood coagulation factors, interferons, and other related drugs. We hope that this review will be of use to many researchers interested in pharmaceuticals derived from biological components, and that it aids in their knowledge of the latest developments in this field.

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Immunohistochemical Localization of Recombinant Human Cu,Zn-SOD(NK341) in Rats after Intravenous Administration.

Tanaka

Tsukamoto

Komatsú

et al. 1995

J. Clin. Biochem. Nutr.

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SummaryTissue and cellular distribution of NK341 (recombinant Cu, Zn-SOD) after intravenous administration in rats was examined by autoradiography and an immunohistochemical technique. Upon observation of the autoradiograms, NK341 was found to be distributed diffusely in well-perfused tissues (liver, heart, kidney, and lung) at 5 min, and subsequently to be concentrated in the kidney cortex. Elimination of NK341 from other tissues was observed at 30 min after administration. These results indicate that NK341 became localized solely in the cortex of the kidney. Radioactivity in the kidney decreased with time, but was still detected even in a small amount at 144 h after administration. In order to examine NK341 distribution in more detail, we performed immunoperoxidase and acid phosphatase staining studies. In the kidney, NK341 was observed in lysosomes of proximal tubule cells, but not detected in glomeruli and other sections. Since the immunoperoxidase method, which should solely detect the antigenic NK341 protein, failed to yield positive staining at 144 h after administration, the remained radioactivity in the kidney at this interval might be attributed to be the existence of metabolites. In the liver and heart, NK341 was detected in Kupffer cells and macrophages, respectively, but not in the hepatocytes or myocytes.

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Metabolic fate of KRN8601: Plasma level, distribution, metabolism and excretion of 125I-KRN8601 after a single intravenous administration to rats.

Cited by 3 publications

References 18 publications

Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation

Raised plasma G-CSF and IL-6 after exercise may play a role in neutrophil mobilization into the circulation

Pharmacokinetics of Biopharmaceuticals: Their Critical Role in Molecular Design

Immunohistochemical Localization of Recombinant Human Cu,Zn-SOD(NK341) in Rats after Intravenous Administration.

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