Pharmacokinetics of Therapeutic Proteins

Lü, Zheng Rong; Sheng, Jennifer; Zhang, Wenhui

doi:10.1002/9783527699124.ch10

Cited by 2 publications

(4 citation statements)

References 100 publications

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“…For pharmacokinetic study of such complex substances derived from animals, the FDA recommends a direct measurement of the pharmacological effect of the drug using the biomarkers approach [28]. Immunoassays and bioassays are among the most useful techniques for this [31]. The bioassay was defended as “an analytical procedure measuring a biological activity of a test substance based on a specific, functional, and biological response of a test system” [32].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach

Shikov

Pozharitskaya²,

Фаустова³

et al. 2019

Marine Drugs

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A glycopeptide fraction (GPF) from internal organs of green sea urchins (Strongylocentrotus droebachiensis Müller, Strongylocentrotidae) has been reported to be an effective bronchitis treatment. In this study, we evaluated the pharmacokinetic and tissue distribution of GPF, following single and repeated intranasal (i/n) administration over the course of seven days in rats. The method measuring lactate dehydrogenase as biomarker was used to analyse the plasma and tissue concentrations of GPF. GPF appears in the plasma 15 min after single i/n administration (100 µg/kg) and reaches its maximum at 45 min. The area under the curve (AUC)0–24 and Cmax were similar using both i/n and intravenous administration, while mean residence time (MRT) and T1/2 after i/n administration were significantly higher compared with intravenous (i/v) administration. The absolute bioavailability of GPF after i/n administration was 89%. The values of tissue availability (ft) provided evidence about the highest concentration of GPF in the nose mucosa (ft = 34.9), followed by spleen (ft = 4.1), adrenal glands (ft = 3.8), striated muscle (ft = 1.8), kidneys (ft = 0.5), and liver (ft = 0.3). After repeated dose administration, GPF exhibited significantly higher AUC0–24 and MRT, indicating its accumulation in the plasma.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach

Shikov

Pozharitskaya²,

Фаустова³

et al. 2019

Marine Drugs

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“…PK involves determining the absorption, distribution, metabolism, and excretion (ADME) of the tested drug [ 43 ]. Larger molecules differ from small molecules in ADME because of higher molecular weight and structural complexity [ 44 ].…”

Section: Pharmacokinetics and Safetymentioning

confidence: 99%

“…For therapeutic polypeptides, metabolism occurs mainly through proteolysis, and the resultant amino acids can be utilized for de novo biosynthesis pathways [ 45 , 60 ]. Mediated by peptidases and proteases, this process is not site-specific and can occur throughout the body [ 43 , 45 ], including common metabolic sites (e.g., liver, kidneys, gastrointestinal tract, blood circulation), other organs and tissues, as well as inside cells [ 43 , 44 , 45 ]. As mentioned earlier, lunasin is highly susceptible to digestion by proteases, thus susceptibility to proteolysis should be investigated for all lunasin therapeutic products to ensure that efficacy is not compromised.…”

Section: Pharmacokinetics and Safetymentioning

confidence: 99%

“…As mentioned earlier, lunasin is highly susceptible to digestion by proteases, thus susceptibility to proteolysis should be investigated for all lunasin therapeutic products to ensure that efficacy is not compromised. Peptides and proteins with low molecular weight (<30 KDa) may undergo renal excretion due to glomerular filtration, although this is also dependent on their structure and net charge [ 43 , 44 , 45 ]. Its physicochemical properties make lunasin prone to renal elimination, and experiments have already detected lunasin in mouse urine [ 28 ].…”

Section: Pharmacokinetics and Safetymentioning

confidence: 99%

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Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy

Souza

Hernández-Ledesma

Souza

2022

IJMS

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Cancer has become one of the main public health problems worldwide, demanding the development of new therapeutic agents that can help reduce mortality. Lunasin is a soybean peptide that has emerged as an attractive option because its preventive and therapeutic actions against cancer. In this review, we evaluated available research on lunasin’s structure and mechanism of action, which should be useful for the development of lunasin-based therapeutic products. We described data on its primary, secondary, tertiary, and possible quaternary structure, susceptibility to post-translational modifications, and structural stability. These characteristics are important for understanding drug activity and characterizing lunasin products. We also provided an overview of research on lunasin pharmacokinetics and safety. Studies examining lunasin’s mechanisms of action against cancer were reviewed, highlighting reported activities, and known molecular partners. Finally, we briefly discussed commercially available lunasin products and potential combination therapeutics.

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Pharmacokinetics of Therapeutic Proteins

Cited by 2 publications

References 100 publications

Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach

Pharmacokinetic Study of Bioactive Glycopeptide from Strongylocentrotus droebachiensis After Intranasal Administration to Rats Using Biomarker Approach

Lunasin as a Promising Plant-Derived Peptide for Cancer Therapy

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